Paul Hutchison
email: p.hutchison@londonmet.ac.uk.

Dominic Abrams

Roberto Gutierrez

G Tendayi

Getting rid of the bad ones: The relationship between group identification, deviant derogation, and identity maintenance

Keywords: Deviance, Black Sheep Effect, Stereotype Change, Social Identity, Group Processes, Exclusion

Two studies investigated the impact of the presentation of an undesirable group member on group stereotype judgments among participants with varying degrees of ingroup identification. In Study 1 (N = 67), identification was associated with stereotype change following presentation of an undesirable, but not a desirable, ingroup member. This relationship was mediated by evaluations of the undesirable ingroup member: the stronger the identification, the more negative the evaluation, and the greater the shift towards a more positive ingroup stereotype. In Study 2 (N = 180), identification was positively associated with ingroup stereotype ratings following presentation of an undesirable ingroup member but was negatively associated with outgroup ratings following presentation of an undesirable outgroup member. As in Study 1, the association between ingroup identification and ingroup stereotype ratings was mediated by evaluations of the undesirable ingroup member. Results are discussed in relation to the black sheep effect and identity maintenance strategies.

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Deviance and identity maintenance 3

The tendency to favor ingroup members over outgroup members is a pervasive but not necessarily inevitable feature of intergroup relations (e.g., [START_REF] Brewer | Ingroup bias in the minimal intergroup situation: A cognitivemotivational analysis[END_REF]Mullen, Brown, & Smith, 1994). In some situations ingroup members display the opposite and favor outgroup members over ingroup members. Research on the 'black sheep' effect [START_REF] Marques | The black sheep effect: Judgemental extremity towards ingroup members in inter-and intra-group situations[END_REF] has showed that desirable ingroup members are favored over similar outgroup members, whereas undesirable outgroup members are favored over similar ingroup members. It has been suggested that devaluation might serve to exclude undesirable members from the representation of the ingroup and protect the group's identity (e.g., [START_REF] Marques | The 'black sheep effect': Social categorization, rejection of ingroup deviates, and perception of group variability[END_REF]. Although this prediction has received considerable circumstantial support from research comparing evaluations of desirable and undesirable ingroup and outgroup members, the link between devaluation and identity maintenance

has not yet been established empirically. The current research aimed to address this limitation. In two experiments we investigated the impact of the presentation of desirable and undesirable group members on perceptions of the group among participants who differed in their level of identification with the ingroup.

Social identity maintenance

According to social identity theory [START_REF] Tajfel | The social identity theory of intergroup behavior[END_REF]), people's identities are derived largely from their memberships in different social categories or groups. When a group membership is salient, individuals evaluate themselves less in terms of their unique and idiosyncratic attributes and more in terms of the comparative properties of the group. To this extent, people are thought to have a basic motivation to see their own groups as superior to outgroups on relevant dimensions.

Excluding undesirable members from the ingroup thus serves the important function of maintaining a positive and distinctive social identity [START_REF] Marques | The 'black sheep effect': Social categorization, rejection of ingroup deviates, and perception of group variability[END_REF].

Support for these ideas comes from several studies showing that desirable ingroup members are evaluated more favorably than identical outgroup members, whereas undesirable ingroup members are evaluated less favorably than identical outgroup members -the 'black sheep' effect (see [START_REF] Marques | The 'black sheep effect': Social categorization, rejection of ingroup deviates, and perception of group variability[END_REF], for a review). Marques and Paez (1994, p. 38) suggested that

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Deviance and identity maintenance 4 devaluation might serve to exclude undesirable members from the representation of the ingroup (see also [START_REF] Eidelman | Responding to deviance: target exclusion and differential devaluation[END_REF]. In this view, the undesirable target is portrayed in such an extremely negative light that he/she can no longer be seen as a typical ingroup member. A presumed consequence of this psychological exclusion is that the overall perception of the ingroup should be enhanced. This follows from research showing contrast and assimilation effects on groupbased judgments following exposure to salient group members. If information about salient group members is included in the representation that is formed when judging the group, the resulting perception of the group will assimilate to that information (e.g., [START_REF] Bless | Context effects in political judgement: Assimilation and contrast as a function of categorization process[END_REF].

Conversely, excluded information produces no assimilation and may be used as a standard against which the group as a whole is judged. Several studies have showed that excluding deviants from the representation of the group has a contrast effect on subsequent group stereotype judgments (e.g., [START_REF] Kunda | When exceptions prove the rule: How extremity of deviance determines the impact of deviant examples on stereotypes[END_REF]. Excluding an undesirable member from the ingroup should therefore enhance the perception of the ingroup's positive stereotypical attributes.

Consistent with this reasoning, [START_REF] Hutchison | Ingroup identification moderates stereotype change in A C C E P T E D M A N U S C R I P T Deviance and identity maintenance 19 reaction to ingroup deviance[END_REF] found that high identifiers expressed a more positive ingroup stereotype after, compared to before, reading about an undesirable ingroup member. High identifiers who read about an undesirable ingroup member also expressed a more positive ingroup stereotype than those presented with a desirable ingroup member, whereas low identifiers' perceptions of the ingroup were unaffected by the target group members. This suggests that high identifiers may have excluded the undesirable member from their representation of the ingroup. This interpretation is supported further by target evaluation ratings, which showed that high identifiers were more negative than low identifiers towards the undesirable ingroup member (see also [START_REF] Castano | Protecting the ingroup stereotype: Ingroup identification and the management of deviant ingroup members[END_REF].

The relationship between group identification, deviant derogation, and identity maintenance

Although these studies suggest that high identifiers may respond to the presence of an undesirable ingroup member with a motivation to protect their group's identity, evidence for the inferred psychological exclusion process remains circumstantial and indirect. Moreover, the

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Deviance and identity maintenance 5 findings from which exclusion is inferred are open to alternative explanation. Group members may derogate an undesirable target extremely but still consider him/her to be a member of the ingroup.

Indeed, high identifiers in [START_REF] Hutchison | Ingroup identification moderates stereotype change in A C C E P T E D M A N U S C R I P T Deviance and identity maintenance 19 reaction to ingroup deviance[END_REF] study may have expressed more dislike for the deviant not necessarily in an attempt to exclude him/her from their representation of the ingroup, but rather because they were more threatened by the undesirable actions of a fellow ingroup member. This threat may also have led high identifiers to enhance their perception of the ingroup's positive stereotypical attributes by way of compensation. To this extent, the inferred link between devaluation and psychological exclusion remains to be established empirically. The current research aimed to address this limitation.

In two studies we assessed the impact of the presentation of an undesirable group member on group stereotype judgments among participants with varying degrees of identification with the ingroup. If devaluation serves to exclude undesirable members from the representation of the ingroup, as traditional explanations of the black sheep effect have argued (e.g., [START_REF] Marques | The 'black sheep effect': Social categorization, rejection of ingroup deviates, and perception of group variability[END_REF], we would expect the level of identification with the ingroup to impact on stereotype change following presentation of an undesirable ingroup member through evaluations of the undesirable ingroup member. If on the other hand devaluation and stereotype enhancement are unrelated to psychological exclusion, then there is no reason to expect target evaluation ratings to mediate the effect of identification on subsequent ratings of the ingroup. In Study 2, we also examined how an undesirable outgroup member might impact on perceptions of the outgroup stereotype. We reasoned that highly identified participants would be more motivated to exclude an undesirable target from the representation they formed when judging the ingroup than from their representation of the outgroup. This difference, we reasoned, should be reflected in ingroup and outgroup stereotype judgments following presentation of an undesirable ingroup or outgroup member, respectively.

Study 1

Method

Participants

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Sixty-seven psychology students from the University of Kent participated as a course requirement. Fifty-five were female and 12 were male.

Materials and Procedure

The study was conducted as part of a research methods lecture. After a brief introduction to the lecture, participants completed four items assessing their level of identification with the group 'psychology students' (from [START_REF] Doosje | Perceived intragroup variability as a function of group status and identification[END_REF]: "I see myself as a psychology student," "I identify with psychology students as a group," "I am pleased to be a psychology student," and "I feel strong ties with psychology students." Responses to these and subsequent items were recorded on rating-scales ranging from 1 (not at all) to 9 (very much). The items were combined (averaged) to form a single group identification score (Cronbach's = .89).

Participants then rated psychologists as a group on a range of positive and negative stereotypical dimensions (from [START_REF] Coull | Protecting the ingroup: Motivated allocation of cognitive resources in the presence of threatening ingroup members[END_REF]: "sensitive,"

"irresponsible," "empathic," "capable of understanding other people's personalities, "unethical", "can be trusted", "unfriendly." The negative items were reverse scored and combined with the positive items to form a single group stereotype score ( = .93). A higher score indicates a more positive stereotype. The questionnaire also included six filler items on topics such as 'career aims' and 'university life' which are not included in the analyses.

Upon completion, the questionnaires were collected by the researcher and participants were informed that the true purpose of the questionnaire was to familiarize them with rating-scales to allow them to participate in a further study at the end of the lecture. Participants were informed that the purpose of the 'second' study was to investigate people's ability to form impressions of individuals on the basis of varying amounts of information. Participants read one of two descriptions of a target psychologist (from [START_REF] Coull | Protecting the ingroup: Motivated allocation of cognitive resources in the presence of threatening ingroup members[END_REF]. Both descriptions began with the same demographic information. The desirable target description continued as follows:

"He very carefully listens to his patients in order to fully understand their problems. He finds the right words to help patients to understand the issues, and expresses a lot of warmth and

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Deviance and identity maintenance 7 empathy when needed. His strong analytical and synthetic skills help him to elaborate solutions and treatments."

In contrast, the undesirable target description continued as follows:

"He tends to see his own problems in the patients' lives. He often interrupts patients because he is nervous, and fails to fully understand their point of view. He lacks the human warmth needed to gain the patients' trust. Finally, he often mixes up patients' records and asks people to explain their problems again and again."

Participants then evaluated the target psychologist using three items: "This person is a good psychologist", "I would like to work with this psychologist", "I would trust this psychologist."

These items were combined to form a single target evaluation score ( = .95). Next, participants recompleted the group stereotype items ( = .93) and were asked to write down any suspicions they might have about the true purpose of the study. No accurate suspicions were recorded. 1

Results

Group stereotype ratings

Our first hypothesis concerned the stereotype ratings. We predicted that ingroup identification would be associated with change towards a more positive ingroup stereotype following presentation of an undesirable ingroup member. We tested this prediction using hierarchical regression analysis. In four steps, we regressed the stereotype ratings recorded after the presentation of the target group members on (1) the pre-presentation stereotype ratings, (2) the standardized identification scores, the target variable (effect-coded -1 = desirable, 1 = undesirable),

(3) the cross products of these variables, and (4) the three-way interaction term. 2 In what follows, the group stereotype ratings are the post-presentation ratings with the pre-presentation ratings controlled for.

The pre-presentation stereotype main effect ( = .79, t[60] = 11.45, p < .001) and the Identification x Target interaction ( = .12, t[60] = 2.03, p = .047) were significant, all other ts < 0.77, ps > .45. The interaction is represented graphically in Figure 1, following procedures outlined

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Deviance and identity maintenance 8 by [START_REF] Aitken | Multiple regression: Testing and interpreting interactions[END_REF]. To test our specific predictions we compared the slopes of the regression lines for identification in both target conditions. Identification was positively associated with stereotype ratings following presentation of an undesirable ingroup member ( = .24, t[33] = 2.87, p = .01, R 2 = .86), whereas there was no association between these variables following presentation of a desirable ingroup member ( = .05, t[30] = .53, p = .60, R 2 = .83). Confirming our prediction, the more participants identified with the ingroup, the more positive they rated the ingroup stereotype after, compared to before, presentation of an undesirable ingroup member.

Target evaluation ratings

To test our second prediction, that identification would be negatively associated with evaluations of an undesirable ingroup member, we regressed the target evaluation scores on the standardized identification scores, the target variable, and the Identification x Target interaction term.

The identification main effect was not significant ( = .11, t [63] = 1.29, p = .20) but the target main effect ( = -.88, t[63] = -15.72, p < .001) and the Identification x Target interaction ( = -.28, t[63] = -.3.40, p = .001) were significant. The relationship between identification and the evaluation scores was negative and significant in the undesirable target condition ( = -.53, t[33] = -3.64, p = .001, R 2 = .29) and positive but not significant in the desirable target condition ( = .23, t[30] = 1.28, p = .21, R 2 = .05). This result showed that the more participants identified with the ingroup, the less favorable they were towards an undesirable ingroup member.

Mediation analyses

Finally, we predicted that identification would have an impact on stereotype change in response to the presentation of an undesirable ingroup member through evaluations of the undesirable ingroup member. To test this hypothesis, we conducted a series of regression analyses using data from the undesirable target condition 3 , following procedures outlined by [START_REF] Baron | The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations[END_REF]. The mediation analysis is represented graphically in Figure 2. As well as the direct effects of identification on the target evaluations and stereotype ratings described above, the

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analyses also revealed that the target evaluations predicted the stereotype ratings ( = -.21, t[32] = -3.25, p = .003), and the direct effect of identification on the stereotype ratings was reduced to a nonsignificant level ( = .14, t[31] = 1.53, p = .14) when the target evaluation scores ( = -.15, t[31] = -2.60, p = .007) were also included as a predictor in the analysis. [START_REF] Sobel | Asymptotic confidence intervals for indirect effects in structural equations models[END_REF] test confirmed that the mediation was significant (z = 2.16, p = .003). 4

Discussion

The results are consistent with predictions. The more participants identified with the ingroup, the more positive they rated the ingroup stereotype after reading about an undesirable ingroup member. This suggests that high identifiers may have excluded the undesirable target from their representation of the ingroup. This interpretation is supported further by the target evaluation ratings, which showed that identification was negatively associated with evaluations of the undesirable ingroup member. Furthermore, mediation analyses confirmed that identification had an impact on the stereotype ratings following presentation of an undesirable ingroup member through evaluations of the undesirable ingroup member: the stronger the identification, the more negative the evaluation, and the greater the shift towards a more positive ingroup stereotype.

Study 2

The results from Study 1 suggest that devaluation might serve to exclude undesirable members from the representation of the ingroup. Study 2 aimed to replicate and extend these findings by also examining how the presentation of an undesirable outgroup member might impact on the perception of the outgroup stereotype. If devaluation indeed excludes undesirable members from the group, then we would expect high identifiers to be more motivated to exclude an undesirable target from the representation they form when judging the ingroup than from their representation of the outgroup. This difference, we reasoned, should be reflected in ingroup and outgroup stereotype ratings following presentation of an undesirable ingroup or outgroup member, respectively. Study 2 was designed to test this prediction.

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One potential limitation to Study 1 was that measuring group ratings both before and after the presentation of a target group member may have created demand characteristics. To reduce this possibility in Study 2, rather than all participants completing the stereotype items twice, half completed the items before the presentation of a target group member and half after the presentation. Additionally, in Study 1 participants indicated their level of identification with the group 'psychology students' before evaluating a 'professional psychologist'. This raises the possibility that participants may not have shared an identity with the target group member, which would undermine our suggestion that devaluation of the undesirable target reflected an identity maintenance strategy. To reduce this possibility in Study 2, the participants and targets were more clearly members of a common category: university students.

Method Participants

Participants were 180 students from the University of Kent. One hundred and forty-nine were female, 29 were male, and two did not specify their gender. Participants' ages ranged from 17

to 57 (M = 20.87, SD = 5.99).

Materials

Cover story and instructions. Participants were informed that the purpose of the study was to assess how students from different universities perceive themselves and each other. They were told that students from the Universities of Kent (UKC) and Essex were participating. Pilot testing indicated that the universities are perceived by UKC students as similar in size and status and that the students are perceived in equally positive stereotypical terms. Specifically, students from both universities are perceived as equally hardworking, ambitious, dedicated, committed, professional, and responsible. Participants were informed that they would be asked to form an image of a target student in order to be able to predict and interpret his future behavior. Responses to all items were made on rating-scales ranging from 1 (not at all) to 9 (very much).

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Group identification measure. Participants completed the same four group identification items from Study 1 to assess their level of identification with their university (α = .82).

Group stereotype measure. Six items measured the perception of UKC or Essex students on a series of positive and negative stereotypical dimensions: 'hardworking,' 'lack ambition,'

'dedicated,' 'lack commitment,' 'professional,' 'irresponsible.' The negative items were reverse scored and combined with the positive items to form a single group stereotype score (α = .92). A higher score indicates a more positive stereotype.

Target descriptions. Participants were presented with one of four descriptions of a target student. The student was either from the University of Kent (ingroup condition) or the University of Essex (outgroup condition). All four descriptions began with the same demographic information and continued to describe the target's attitude toward and commitment to his work, his ambitions, and so on. The target student either confirmed (desirable target condition) or disconfirmed (undesirable target condition) the positive stereotype of students. Examples of sentences used to describe the desirable student included the following: "He regularly attends lectures, never missed exams, and friends often rely on him for information," and "[He] has the intellectual ability to successfully complete the degree course and also the required dedication and motivation." When asked to comment on his outlook, the desirable student responded as follows: "I came here primarily to study, but also to have fun and meet new people. It is important to get the balance between work and play right."

In contrast, examples used to describe the undesirable student included the following: "He fails to attend lectures regularly, often missed exams, and relies on classmates for information," and "[He] has the intellectual ability to successfully complete the degree course but he lacks the required dedication and motivation." When asked to comment on his outlook, the undesirable student responded as follows: "I came here to have fun and meet new people, not to spend my time studying. There are better things for young people to do with their time than read books."

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Target evaluation measure. Three items measured participants' evaluation of the targets: "I like this student's outlook," "This person is a good student," "I would like to work with this student." These items were combined to form a single target evaluation score (α = .87).

Procedure

The study was conducted in a lecture room. Participants were randomly assigned to conditions. All participants first completed the identification items. Half of them completed the stereotype items before reading the target description. Those participants then evaluated the target.

The other half read the target description, completed the stereotype items, and evaluated the target.

Debriefing took place in the following lecture.

Results

Group stereotype ratings

We predicted that identification with the ingroup would correlate positively with ingroup stereotype ratings following presentation of an undesirable ingroup member. We tested this prediction using hierarchical regression analyses. In four steps we entered (1) the predictors group (effect-coded -1 = ingroup, 1 = outgroup), target (effect-coded -1 = desirable, 1 = undesirable), time of judgment (effect-coded -1 = pre-manipulation, 1 = post-manipulation) and the standardized group identification scores, (2) the pairwise products of these predictors, (3) the three-way interaction terms, and (4) the product of all predictors to test the four-way interaction.

The four-way interaction was significant ( = -.48, t[164] = -2.08, p = .039, all other ts < 1.36, ps > .17). To test our specific hypotheses we compared the slopes of the regression lines for identification across all combinations of group and time of judgment in both target conditions (see Figure 3). The slopes were not significant in the desirable target condition (all ts < 1.16, ps > .26).

In the undesirable target condition, identification was positively associated with ingroup stereotype ratings after ( = .40, t[21] = 2.01, p = .06, R 2 = .16), but not before ( = .02, t[18] = .07, p = .95, R 2 < .001), the presentation of an undesirable ingroup member. In contrast, identification was negatively associated with outgroup stereotype ratings after ( = -.48, t[21] = -1.98, p = .061, R 2 =

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.16), but not before ( = .09, t[22] = .41, p = .69, R 2 = .01), the presentation of an undesirable outgroup member. These results indicated that the more participants identified with the ingroup, the more positive they rated the ingroup stereotype following the presentation of an undesirable ingroup member, and the more negative they rated the outgroup stereotype after reading about an undesirable outgroup member.

Target evaluation ratings

The target evaluation ratings were also analyzed using hierarchical regression analysis. In three steps we entered (1) the independent variables, (2) their cross products, and (3) the three-way interaction of Identification x Target x Group. The analysis revealed a significant main effect of target ( = -.84, t[172] = -23.33, p < .001), a significant Group x Identification interaction ( = .08, t[172] = 2.31, p = .02), and a significant Group x Target interaction ( = .17, t[172] = 4.83, p < .001). These effects were qualified by a significant Identification x Group x Target interaction ( = .16, t[172] = 4.54, p < .001; all other ts < 1, ps > .45).

To establish whether the familiar black sheep effect emerged [START_REF] Marques | The black sheep effect: Judgemental extremity towards ingroup members in inter-and intra-group situations[END_REF], we decomposed the significant Group x Target interaction by comparing the slopes of the regression lines for group in both target conditions. The slope was negative in the desirable target condition ( = -.31, t[88] = -3.10, p = .003, R 2 = .10) and positive in the undesirable target condition ( = .34, t[88] = 3.33, p = .001, R 2 = .11). This indicated that participants favored a desirable ingroup member over a desirable outgroup member, but favored an undesirable outgroup member over an undesirable ingroup member. Thus, the black sheep effect was established.

To test our prediction that identification with the ingroup would predict evaluations of desirable and undesirable ingroup and outgroup members, we decomposed the significant Identification x Group x Target interaction by comparing the slopes of the regression lines for identification across all combinations of group and target. Identification was positively associated with evaluations of the desirable ingroup member ( = .31, t[46] = 2.23, p = .03, R 2 = .10), whereas the relationship between identification and evaluations of the desirable outgroup member was not

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Deviance and identity maintenance 14 significant ( = -.08, t[40] = -.51, p = .62, R 2 = .01). In contrast, identification was negatively associated with evaluations of the undesirable ingroup member ( = -.56, t[41] = -4.28, p < .001, R 2 = .31), whereas the relationship between identification and evaluations of the undesirable outgroup member was positive but not significant ( = .25, t[45] = 1.70, p = .10, R 2 = .06). This confirmed that the more participants identified with the ingroup, the more favorable they were towards a desirable ingroup member and the less favorable they were towards an undesirable ingroup member.

Mediation analyses

As in Study 1, we predicted that the relationship between ingroup identification and ratings of the ingroup stereotype following the presentation of an undesirable ingroup member would be mediated by evaluations of the undesirable ingroup member. To test this prediction we conducted a series of regression analyses using data from the ingroup undesirable target condition [START_REF] Baron | The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations[END_REF] 5 . The mediation analysis is represented graphically in Figure 4. As well as the abovedescribed effects of identification on the target evaluations and group stereotype ratings, the regression analyses also confirmed that the target evaluations predicted the stereotype ratings ( = -.53, t[21] = -3.73, p = .001), and the direct effect of identification on the stereotype ratings became non-significant ( = .09, t[20] = .45, p = .65) when the target evaluation scores ( = -.48, t[20] = -2.86, p = .01) were included in the analysis. A Sobel test confirmed that the mediation was significant (z = 2.03, p = .04). 6

Discussion

The results are again consistent with predictions. Participants favored a desirable ingroup member over a desirable outgroup member, but favored an undesirable outgroup member over an undesirable ingroup member, consistent with the black sheep effect [START_REF] Marques | The black sheep effect: Judgemental extremity towards ingroup members in inter-and intra-group situations[END_REF].

Additionally, identification with the ingroup was positively associated with ingroup stereotype ratings following the presentation of an undesirable ingroup member but was negatively associated with outgroup ratings following presentation of an undesirable outgroup member. As in Study 1, the

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Deviance and identity maintenance 15 relationship between ingroup identification and ingroup stereotype ratings was mediated by evaluations of the undesirable ingroup member: the stronger the identification, the more negative the evaluation, and the greater the shift towards a more positive perception of the ingroup stereotype.

General Discussion

Our starting point was the assumption, following traditional explanations of the black sheep effect (e.g., [START_REF] Marques | The 'black sheep effect': Social categorization, rejection of ingroup deviates, and perception of group variability[END_REF], that high identifiers would be motivated to exclude an undesirable member from their representation of the ingroup. We reasoned that excluding an undesirable member from the ingroup would have a contrast effect on subsequent perceptions of the ingroup stereotype. Consistent with this, in both studies we found that ingroup identification had an impact on the ingroup stereotype ratings following the presentation of an undesirable ingroup member through the target evaluations ratings.

In Study 2, participants were more negative towards an undesirable ingroup member than an identical outgroup member, and only when the undesirable target was an ingroup member did the target evaluation scores mediate the impact of identification on the stereotype ratings. Thus, although the undesirable ingroup and outgroup members were devalued relative to their desirable counterparts, it seems that devaluation was related to psychological exclusion only when the undesirable target was an ingroup member. When the undesirable target was an outgroup member, the stronger the ingroup identification, the greater was the shift towards a more negative outgroup stereotype. This suggests that high identifiers were more motivated to include an undesirable target in the representation they formed when judging the outgroup. It may be that including an undesirable member in the representation of the outgroup allows high identifiers to establish or maintain a positive distinction between the ingroup and the outgroup (see Abrams, Marques, Randsley de Moura, [START_REF] Abrams | The maintenance of entitativity: A subjective group dynamics approach[END_REF].

The current research extends our understanding of the social cognitive processes that might underlie the familiar black sheep effect [START_REF] Marques | The black sheep effect: Judgemental extremity towards ingroup members in inter-and intra-group situations[END_REF]. The results suggest that high

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Deviance and identity maintenance 16 identifiers were more extreme in their devaluation of an undesirable ingroup member because they were more motivated to exclude that member from their representation of the ingroup. If the negative evaluations were not driven by a motivation to exclude the undesirable target from the ingroup, then there is no reason why the target evaluation ratings should have mediated the effect of identification on the ingroup stereotype ratings. Our results suggest that high identifiers were indeed motivated to exclude the undesirable target from the ingroup, and so the more they devalued the undesirable ingroup member, the more positive they perceived the ingroup stereotype.

Although the results are consistent with our predictions, it is important to address some potential limitations with the research. One concern is the possibility that the results may have been biased by demand characteristics. This may be a concern especially in Study 1, in which participants completed the same stereotype items both before and after reading about a target group member. However, there are various reasons to believe that demand characteristics did not influence the results. First, the presentation of a desirable target had no effect on the group ratings.

A demand account would have to explain why the presentation of an undesirable target would produce a demand but not the presentation of a desirable target. Second, only high identifiers modified their perceptions of the group stereotype following the presentation of an undesirable group member. A demand account would have to explain why participants with different levels of identification would react differently to what would appear as a demand of the experiment. Third, similar results were obtained in Study 2, in which half the participants completed the stereotype items before the presentation of a target group member and half after the presentation. Finally, none of the participants expressed any accurate suspicions about the true aims of the research. For these reasons, we are confident that demand characteristics did not bias the results. Nevertheless, future research should aim to replicate the effects using different paradigms.

It should also be noted that in both studies, the level of ingroup identification did not predict the group ratings taken before the presentation of the target group members or following the presentation of a desirable ingroup or outgroup member. This may seem at odds with the

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Deviance and identity maintenance 17 assumption that high identifiers will use every opportunity to perceive the ingroup in a positive light. However, the results align with previous research showing that it is only when the ingroup is threatened that the level of identification with the ingroup becomes a reliable predictor of groupbased judgments and evaluations (e.g., [START_REF] Hutchison | Protecting threatened identity: Sticking with the group by emphasizing ingroup heterogeneity[END_REF].

Additionally, like previous research on the black sheep effect (see [START_REF] Marques | The 'black sheep effect': Social categorization, rejection of ingroup deviates, and perception of group variability[END_REF], the 'deviants' in our research were intentionally portrayed as undesirable and unfavorable. However, several studies have suggested that perceptions of deviance can change across different social contexts, to the extent that an individual that is seen as being deviant in one context need not necessarily be deemed deviant in another context (e.g., [START_REF] Matheson | Dissidence from within: Examining intragroup reactions to attitudinal opposition[END_REF]. An interesting avenue for future research is to assess how the same target person might impact on perceptions of their group in different comparative contexts.

In conclusion, the results from two studies are consistent with traditional interpretations of the black sheep effect, which have argued that in derogating undesirable ingroup members, high identifiers would attempt to protect the ingroup by "getting rid of the bad ones" (Yzerbyt, Castano, Leyens, & Paladino, 2000, p. 267). While this interpretation has received considerable circumstantial support from research comparing evaluations of desirable and undesirable ingroup and outgroup members, the current research is the first to establish empirically the relationship between group identification, deviant derogation, and identity maintenance.

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Deviance and identity maintenance 20 Footnotes 1. An accurate suspicion was defined a priori as one suggesting that the aim of the research was to assess how exposure to a target group member might influence group ratings (or vice-versa).

The majority of participants reported no suspicions.

2. When analyzing pre-test/post-test data in this way it is important to test the assumption of homogeneity of regression. This is the assumption that the slopes of the regression of the dependent variable on the covariate (pre-presentation group stereotype ratings) are the same for all combinations of the independent variables (identification and target). If the covariate does not interact with the independent variables, then the assumption has not been violated. None of the interactions involving pre-presentation stereotype ratings was significant. Additionally, there were no apparent non-normalities in the residuals and no multivariate outliers.

3. We did not conduct a mediation analysis using data from the desirable target condition because the conditions for mediation to be present were not satisfied in that condition.

4. The mediation analysis suggests that differences in the group stereotype ratings associated with the level of identification were a result of evaluations of the undesirable target. However, it is theoretically possible that differences in the group ratings associated with identification impacted on the target evaluations. That is, the presentation of an undesirable ingroup member may have had an impact on the representation of the group, which in turn may have led to harsher treatment of the target. To explore this possibility we tested an alternative model which reversed the roles of the target evaluations and group stereotype ratings. In this model identification was the independent variable, target evaluation was the dependent variable, and the group stereotype score was the mediator. The data did not support this model. After controlling for the stereotype scores the effect of identification on the target evaluation scores remained significant ( = -.44, t[31] = -2.23, p =

.03) and a Sobel test indicated that mediation had not occurred (z = 1.67, p = .10).

5. As in Study 1, we conducted a mediation analysis on data from the undesirable condition only because the conditions for mediation to be present were not satisfied in the other conditions.

Figure 2 .Figure 3 .

 23 Figure captions

The research reported in this article was supported by funding from the Economic and Social Research Council (R42200034207). The authors are grateful to Jeff Stone and two anonymous


Imran Aziz

Kate E Evans

Andrew D Hopper

David M Smillie

David S Sanders

A prospective study of the aetiology of lymphocytic duodenosis

Keywords: Coeliac disease < Disease-based, Irritable bowel syndrome < Disease-based, Stomach and duodenum < Organ-based, H. pylori < Topics, Histopathology < Topics, NSAIDs < Topics, Clinical pharmacology < Topics

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

We thank the reviewers for their comments, which we feel has improved this manuscript. We hope we have addressed the reviewers comments appropriately.

Reviewer: 1 1. Comments for Transmission to the Authors The title is rather meaningless and the histological parameters should be defined from the outset -i.e. in the abstract -do you not mean lymphocytic duodenosis -normal architecture and intraepithelial lymphocytes>25/ 100 enterocytes? If so then say so!-I would suggest you discuss this with the histopathologists who made the diagnosis and include them in this work and on the authorship Comment 1a: We have now changed the title to the one suggested by the reviewer which we hope reflects this study more accurately. 'A prospective study of the aetiology of lymphocytic duodenosis.' Title page 1 top line 'A prospective study of the aetiology of lymphocytic duodenosis.' Comment 1b. Lymphocytic duodenosis was diagnosed exactly on the basis that the reviewer 1 suggested: lymphocytic duodenosis = normal architecture and intraepithelial lymphocytes>25/ 100 enterocytes. We clarified this with our 3 GI pathologists as suggested. We have also now stated that in our study group that lymphocytic duodenosis = normal architecture and intraepithelial lymphocytes>25/ 100 enterocytes. Page 2 -1 st paragraph, page 3 -3 rd paragraph : Lymphocytic duodenosis (LD) is defined by normal villous architecture and intraepithelial lymphocytes (IELs) >25 per 100 enterocytes Comment 1c. With regards to the 3 GI pathologists who work with us -we have now acknowledged them in the manuscript. Page 1: "We wish to acknowledge the help of Professor TJ Stephenson, Dr SS Cross and Dr A Dube (Department of GI Histopathology, Royal Hallamshire Hospital, UK) who were all involved in the reporting and review of these cases".

2. Define the background -I'd hardly define a retrospective review of 124 patients as "case reports", use the term previous retrospective studies… (see Vande Voort et al below). Comment 2: We are sorry that we did not fully acknowledge Vande Voort et al study in the abstract and that the abstract could be misleading. For this reason we have now changed the abstract background from ''case reports" to "previous retrospective studies" -page 2-1 st Method: One hundred patients with lymphocytic duodenosis were rigorously investigated for coeliac disease and other known associations for LD by initial investigations of coeliac serology, and exclusion of infection. Of 34 with no explanation for LD, 29 underwent repeat duodenal biopsy following gluten challenge.

Results: Coeliac disease was present in 16% of patients with LD. In the absence of a positive coeliac diagnosis, LD was most commonly associated with drugs (21%), infection (19%), immune dysregulation (5%) inflammatory bowel disease (2%), microscopic colitis (2%) and IgA deficiency (1%). Of 34 with no known associations, 18/34 had symptoms of irritable bowel syndrome and in 29 patients investigated with repeat duodenal biopsy the IEL count returned to normal in 22. Conclusions: In 66% of cases of LD, a known association can be found by further investigation; importantly 16% will have coeliac disease. In those with no apparent cause, there may be an association with IBS and the IEL count became normal on repeat biopsy in 22%.

Comment 4: We have now taken all the reviewer 1 comments on the structure and content of this abstract and incorporated into our paper "Abstract Background: Lymphocytic duodenosis (LD) is defined by normal villous architecture and intraepithelial lymphocytes (IELs) > 25 per 100 enterocytes. Such patients should not be diagnosed with coeliac disease, solely by histology, as previous retrospective studies have suggested other associations with LD.

Aim: A prospective study of the aetiology of LD.

Method: One hundred patients with LD were rigorously investigated for coeliac disease and other known associations for LD by initial investigations of coeliac serology, and exclusion of infection. Of 34 with no explanation for LD, 29 underwent repeat duodenal biopsies following a gluten challenge.

Results: Coeliac disease was present in 16% of patients with LD. In the absence of a positive coeliac diagnosis, LD was most commonly associated with drugs (21%), infection (19%), immune dysregulation (4%) inflammatory bowel disease (2%), microscopic colitis (2%), sarcoidosis (1%) and IgA deficiency (1%). Of 34 with no known associations, 18/34 had symptoms of irritable bowel syndrome (IBS) and in 29/34 patients investigated with repeat duodenal biopsies the IEL count returned to normal in 22.

Conclusions: In 66% of cases of LD, a known association can be found by further investigations; importantly 16% will have coeliac disease. In those with no apparent cause, there may be an association with IBS and the IEL count became normal on repeat biopsy in 76%." See full abstract page 2 [START_REF] Voort | Lymphocytic duodenosis and the spectrum of coeliac disease[END_REF] The investigators described features which would help to discriminate patients with LD who had underlying coeliac disease from those who did not, for example the presence or absence of HLA DQ2 or DQ8. However they did not systematically investigate these patients for other causes of LD." Page 3, paragraph 3 8a. The early recognition of celiac disease is clearly recommended in 2009 NICE guidelines http://www.nice.org.uk/nicemedia/pdf/CG86FullGuideline.pdf This should be read and cited appropriately.

Comment 8a-We agree and have incorporated NICE into the revised manuscriptreference 27.

8b. HLA typing is expensive -and serology is the first line investigation. If this is negative and you still strongly suspect celiac disease HLA typing can help, but this is not a first line investigation. This should be stated. The serology paragraph should precede this. Comment 8b-We agree and have moved the serology paragraph so that it precedes the HLA paragraph. In addition we have stated that HLA is not a first line test: Please see pages 4 (2 nd paragraph) running through to page 5 "Investigations to support the diagnosis of coeliac disease should involve testing for tissue transglutaminase antibody (tTG) and/or endomysial antibody (EMA) in the presence of a normal IgA level. [START_REF]Coeliac disease: recognition and assessment of coeliac disease[END_REF] However, patients with LD with possible/potential coeliac disease may present with a negative EMA, as the prevalence of a positive EMA strongly correlates with the severity of mucosal damage. [START_REF] Tursi | Low prevalence of antigliadin and antiendomysium antibodies in subclinical/silent coeliac disease[END_REF] For cases where the diagnosis is uncertain (such as in patients with LD) there may be a role for human leucocyte antigen (HLA) typing [START_REF]Coeliac disease: recognition and assessment of coeliac disease[END_REF] -HLA DQ2 or DQ8 are closely linked with coeliac disease, occurring in up to 98% of cases, [START_REF] Sollid | Evidence for a primary association of coeliac disease to a particular HLA-DQ alpha/beta heterodimer[END_REF] but they are also present in 25% of the normal population. [START_REF] Murdock | Diagnostic criteria for coeliac disease: time for change?[END_REF] An absence of these haplotypes can therefore be used as a negative predictive test. Approximately 50% of patients with LD have been shown to be negative for HLA DQ2 or DQ8, thus not belonging to the spectrum of coeliac disease. [START_REF] Voort | Lymphocytic duodenosis and the spectrum of coeliac disease[END_REF] HLA typing is expensive and should be reserved for equivocal cases. If the serology is negative and you still strongly suspect coeliac disease HLA typing can help, but it is not a first line investigation. A recent Finnish study has shown that patients with LD who have both a positive EMA and HLA to belong to the spectrum of coeliac disease. The investigators randomised these patients to either a gluten containing diet (n=10) or GFD (n=13), and found progressive clinical, biochemical and histological deterioration in all those randomised to a gluten containing diet. Furthermore these individuals improved all parameters when they were commenced on a GFD, after the initial study period. [START_REF] Kurppa | Diagnosing mild enteropathy coeliac disease: a randomized, controlled clinical study[END_REF] A gluten challenge can also be useful in causing further mucosal deterioration in those patients with potential coeliac disease in whom the initial small intestinal biopsies reveal only minor abnormalities. [START_REF] Wahab | Gluten challenge in borderline glutensensitive enteropathy[END_REF] However, an initial trial response to a GFD is not as helpful, as up to 38% of patients with LD who have had a favourable response to a GFD are negative for the DQ2 or DQ8 haplotypes. [START_REF] Voort | Lymphocytic duodenosis and the spectrum of coeliac disease[END_REF] 9. Aim: was this not to develop a systematic approach to diagnose the underlying cause of LD and treat patients effectively? Comment 9-We have now changed the aim to what has been suggested by reviewer 1 Previous: For these reasons the aim of our study was to develop a systematic and prospective approach towards investigating patients with raised IELs, thereby enabling a means to detect and be aware of the prevalence figures for the underlying causes. New: For these reasons the aim of our study was to develop a systematic approach to diagnose the underlying cause of LD and treat patients effectively. Page 5, last paragraph 10. Methods Did you go back to the files at a time point to do this study or has it been ongoing from 2003? If you went back it is retrospective study surely? Did you only have 100 cases of LD in seven years? or did you only recruit patients who agreed to participate in the study? And therefore what is the prevalence of this condition in your unit? Comment 10-The senior author of this paper (David Sanders) was initially involved in a study where the investigators described that the prevalence of LD was 2% (ref 8-Hopper AD, Hadjivassiliou M et al, Senior Author Sanders DS. What is the role of serologic testing in coeliac disease? A prospective, biopsy-confirmed study with economic analysis. Clin Gastroenterol Hepatol. 2008 Mar;6(3):314-20.). Based on that initial clinical study -Prof Sanders then started to adopt a systematic approach to the investigation of these patients since 2003. Prof Sanders undertakes a gastroscopy list every week with 10 patients undergoing gastroscopy. Over a 7 year period performing 400 gastroscopies per year (40 weeks of practice x 10 gastroscopies) if 2% of these cases have LD (as previously reported then he has seen 2% of 2800 = 56 cases of LD. More recently (in the last few years) other colleagues have also been referring LD patients to him for further evaluation. We hope this accounts for the 100 patients prospectively recruited in this study. We did not have any patients who did not want to take part in this study -however, there were some who had the initial tests and then declined the 2 nd gastroscopy as we have already mentioned in the results section 11) As I understand the study was conducted in two stages:

Step 1 -The cause of LD available from history and investigations performed around the time of the first endoscopy?

Step 2 -if no apparent cause, gluten challenge, investigation of GI infections (including H. pylori) -for those who had not had Hp status established at time of repeat endoscopy did you check that they had not taken eradication therapy in the intervening period -and how long was this? Comment 11 -We are sorry if this is confusing. After patients were recognised as having LD (following their first endoscopy) we then questioned them for symptoms and tried to establish if they had ever had H.Pylori testing (in primary care or elsewhere). At the time of their second endoscopy (which was 6 weeks to 3 months later) we would then take a CLO test for H.Pylori.

12) If the intervening period was some time from the original biopsy did you reevaluate symptoms at the time of rebiopsy? Yes we did. We have now incorporated this additional information: Comment 12 -'This involved a six week gluten challenge followed by repeat coeliac serology, duodenal biopsies and small bowel aspirate for microscopy, culture and sensitivity. If no previous H.pylori status was documented then patients where questioned for symptoms at the time of second biopsy and a CLO test was also performed." Page 6, line 13-16

Results

These are poorly presented and would be better served as follows a) In 100 patients, an underlying cause for LD was found in 66%, principally drug related (21%) and 16% had coeliac disease, of 5 cases of infection these were …… And similar for immune dysregulation -is this not autoimmune disease and separately sarcoidosis….. Of 22 /29 patients who were willing to undergo re-biopsy, in the IEL was reduced to <25/ 100 enterocytes on the second biopsy, whilst 7 had a persistently raised count with no apparent cause….. How many needed a two step approach to find an underlying cause? Comment 13 -We have now addressed all these issues: "In order to find an underlying cause, 88/100 patients had to be investigated using the two-step approach. In these 100 patients, an underlying cause for LD was found in 66%, principally drug related (21%), coeliac disease (16%) and H. Pylori (14%). There were 5 cases of gastrointestinal infection: giardia, threadworms, campylobacter and two cases of small bowel bacterial overgrowth. There were 4 cases of autoimmune disease including systemic sclerosis, hypothyroidism, rheumatoid arthritis and primary biliary cirrhosis. There was one case of sarcoidosis. Detailed causes of LD are shown in figure 2. All cases of coeliac disease were positive for HLA DQ2 or DQ8, whereas 47/84 noncoeliac cases carried the DQ2 or DQ8 haplotypes (p = 0.0004). Despite an extensive work up, in 34 cases we were unable to identify a cause for the raised IELs. Of these, 29 /34 patients were willing to undergo re-biopsy. In 22/29 the IEL count was reduced to < 25 per 100 enterocytes on the second biopsy, whilst 7 had a persistently raised count with no apparent cause. When questioning these 34 patients, 18 had gastrointestinal symptoms consistent with a diagnosis of irritable bowel syndrome (IBS) using the ROME II Criteria. [START_REF] Thompson | Functional bowel disorders and functional abdominal pain[END_REF]" Page 7 -results section 14) What was the range of IEL counts? -i.e did those who "normalised" have 26/27/28 and in all biopsies? to start with and were higher counts seen in coeliacs for example -the count range should be stated and correlated with causes -were the actual counts stated in reports or do you need to revisit this? Comment 14: Unfortunately we have not performed quantitative analyses beyond indentifying patients who have LD. Our GI pathologists comment on LD as previously defined but do not give an absolute count. However, Kakar's study (ref 9) has previously shown no significant difference in IEL counts between coeliacs versus non-coeliacs. 15) Therefore in 34%, no cause was apparent, although 18 in this group (18% overall) had symptoms of IBS. Comment 15-We agree with this and have now addressed this in the text: (results last paragraph page 7) "Despite an extensive work up, in 34 cases we were unable to identify a cause for the raised IELs. Of these, 29/34 patients were willing to undergo re-biopsy. In 22/29 the IEL count was reduced to <25 per 100 enterocytes on the second biopsy, whilst 7 had a persistently raised count with no apparent cause. When questioning these 34 patients, 18 had gastrointestinal symptoms consistent with a diagnosis of irritable bowel syndrome (IBS) using the ROME II Criteria. 34" 16) Discussion: Is the first sentence really true? It is not clear from the method how the patients were recruited -please clarify this before making this statement. Comment 16-Yes the first sentence is correct but we have clarified this in the methods: "The study was conducted between the periods February 2003 to February 2010 at the Royal Hallamshire Hospital in Sheffield, a tertiary care centre for gastroenterology. One hundred patients with LD (> 25 IELs per 100 enterocytes) were sequentially identified and investigated to determine a cause for their raised IELs. All patients that were identified agreed to participate. The study was registered with both South Sheffield local ethics and audit committees." -page 6, paragraph 1 17) In the discussion on no apparent cause the range of counts should be discussed, IELs are dynamic and the idea of a post infective picture is good -did you explore this clinically with these patients? Comment 17 -Unfortunately we have not performed quantitative analyses beyond indentifying patients who have LD. Our GI pathologists comment on LD as previously defined but do not give an absolute count. However, Kakar's study (ref 9) has previously shown no significant difference in IEL counts between coeliacs versus non-coeliacs. We think that this will be the next step in our work but unfortunately do not have that data presently. For this reason we have not discussed this intimately. 'The significance and association of IELs and IBS is contentious. Studies have shown conflicting data, with reported IEL counts ranging from normal to slightly elevated. 36- 44 18) The conclusion could include an algorithm for finding the underlying cause in LD with an emphasis on doing coeliac serology and taking a comprehensive history. Is HLA typing on all feasible? Comment 18 : We have now included an algorithm as part of the method section and addressed this in the conclusion. See algorithm page 10 "In conclusion, in 66% of cases of LD, a known association can be found by further investigation; importantly 16% will have coeliac disease. HLA typing may have a role in differentiating between coeliac and non-coeliac cases. [START_REF]Coeliac disease: recognition and assessment of coeliac disease[END_REF] In those with no apparent cause, there may be an association with IBS and the IEL count became normal on repeat biopsy in 76%" -page 9, last paragraph 19) There are irritating grammatical errors throughout. Comment 19-We apologise for this and hope that the revised manuscript has corrected this problem Reviewer: 2 Comments for Transmission to the Authors Major points: 20) The authors address an important question, which has surprisingly not been investigated prospectively until now. However, the study has several limitations and mainly has to be rewritten to address some questions more precisely. Especially, the point how long patients were followed, has to be addressed, if possible (further outcome).

Comment 20 -Of the 100 patients investigated 74 were women. The age range was from 16 to 83, with a median age of 47. The mean period of follow up was 18 months (range 2-72). Added to the results section page 7, paragraph 1 21) How was CD defined? Further deterioration of Marsh status? Only together with positive serology? Only, when Marsh status normalized after GFD? This has to be clarified, actually at the beginning of the study. Has this been done? How was CED defined (including data from capsule endoscopy)? Comments 21: All patients at the end of step 1 where there was a suspicion of coeliac disease or no clear cause, proceeded to step 2, involving a 6 week gluten challenge with repeat coeliac serology and duodenal biopsies. "A diagnosis of coeliac disease was made in those with positive serology (EMA or TTG), relevant symptoms and an HLA pattern of DQ2 or DQ8. These patients also had to have either progression of their LD to villous atrophy or a persistence of their LD. Finally in these individuals we also ensured that they had a symptomatic response to the GFD." This has been added to the method section page 6, 3rd paragraph 22) How was CED defined (including data from capsule endoscopy)? Comment 22) We presume that CED is coeliac disease. We did not perform capsule endoscopy on all our patients. 23) I miss the statistical methods. We are sorry that we had not incorporated this: Comment 23 -"Statistical analyses of data were performed using SPSS. Differences between the groups were assessed using Fisher's Exact Test." We have added this to the methods section -page 6, final paragraph Minor points: Abstract: 24) I personally would omit the note that this is the first prospective trial in the abstract, but actually would state that another method to categorize increased IELs was investigation of concomitant medications, follow-up of patients including repeat biopsy, investigation for IgA-deficiency, search for microscopic colitis and concomitant gastrointestinal infections. Comment 24 -The revised abstract now reads as-Aim: A prospective study of the aetiology of lymphocytic duodenosis This is in line with the 1 st reviewer. We hope that this is acceptable to the second reviewer and editorial board. We have made this decision because the study is prospective but also because this was a major revision for the 1 st reviewer but listed as a minor point by the second reviewer. 25) I would suggest to use the pharmacological name of aspirin. At least in some countries "aspirin" is only used by certain companies. Comment 25-We have now changed this accordingly using acetylsalicylic acid (ASA) Introduction: 26) What is meant with antigenic challenges in contrast to antigenic stress? Please, clarify. Please use past consequently (page 3, line 37; page 5, line 18) and also in M and M..... Comment 26 -We are sorry for this confusion and have now changed this in the text -page 3, line 2 27) page 4, line 18: Where do we know that immune dysregulation is the reason for increased IEL counts in thyroid .. disease? In the case of uncertainty omit this speculation. Comment 27-There are 2 previous studies (ref 9,13) which have used the term immune dysregulation and described patients in a similar way. Nevertheless we agree that this is speculative and have stated this in the text "However, conditions such as thyroid disease, rheumatoid arthritis, psoriasis and connective tissue disorders can cause raised duodenal IEL counts independently through a process of immune dysregulation [START_REF] Kakar | Significance of intraepithelial lymphocytosis in small-bowel biopsy samples with normal mucosal architecture[END_REF][START_REF] Michaëlsson | Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin[END_REF] -this could be viewed as a speculative opinion and further work is required to delineate this relationship." -page 4, line 8 "The concept of immune dysregulation causing LD has previously been noted and is poorly understood, possibly even speculative. [START_REF] Kakar | Significance of intraepithelial lymphocytosis in small-bowel biopsy samples with normal mucosal architecture[END_REF][START_REF] Michaëlsson | Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin[END_REF] Of the 4 cases in our study where LD was attributed to immune dysregulation, all went through step 2 to ensure that both coeliac disease and gastrointestinal infections were excluded." -page 8, paragraph 3 28) Has CD been excluded completely in these cases? Yes we did exclude CD based on the definition of CD in our methods section Comment 28-"A diagnosis of coeliac disease was made in those with positive serology (EMA or TTG), relevant symptoms and an HLA pattern of DQ2 or DQ8. These patients also had to have either progression of their LD to villous atrophy or a persistence of their LD. Finally in these individuals we also ensured that they had a symptomatic response to the GFD." -page 6, 3rd paragraph 29)Dermatitis herpetiformis is not only frequently associated with CD, but almost in 100 % associated with CD.... (cite publication). Comment 29-We have now changed this accordingly "Also dermatitis herpetiformis (DH), an itchy blistering rash, is almost always associated with coeliac disease, [START_REF] Fry | Dermatitis herpetiformis[END_REF] with up to 50% of patients demonstrating only subtle mucosal changes on duodenal biopsy. 23,24" M and M 30) In case of H. pylori infection as causative agent or bacterial overgrowth: was IEL count tested after treatment of underlying cause and had the IEL count normalised? Was normalisation of IEL count after treatment of underlying cause prerequesite for diagnosing this as underlying cause? In what time interval was H. pylori eradication tested?

Comment 30: H.pylori has previously been shown to cause raised IELs with levels being shown to decrease (not necessarily normalise) post eradication -ref 17,18. We did not count pre and post eradication levels as this was not the aim of our study. Based on the previously available data we accepted H. Pylori as a cause for LD (ref 17,18). We undertook repeat assessments within 6-12/52 of patients following eradication therapy. In those patients who agreed to have a further biopsy -the LD normalised.

31) How was inflammatory bowel disease diagnosed? Please, state this (Crohn´s disease or ulcerative colitis). Was there a special endoscopic or histologic feature in the endoscopies/ biopsies of these two patients? Comment 31 -UC was diagnosed on the basis of colonic biopsies which revealed mucosal inflammation and Crohn's was base on the second duodenal biopsy revealing granulomatous changes. Results page 7 lines 9-13. 33. How was irritable bowel disease defined (special questionaire)? Comment 33 -We used the ROME II criteria and have added this-"When questioning these 34 patients, 18 had gastrointestinal symptoms consistent with a diagnosis of irritable bowel syndrome (IBS) using the ROME II Criteria. 34" Page 7 last line 34) Discussion: Overall the discussion is somewhat short and eg the hypothesis of immune dyregulation is not discussed at all as well as the CED patients . Comment 34 -We have added a paragraph on immune dysregulation "The concept of immune dysregulation causing LD has previously been noted and is poorly understood, possibly even speculative. [START_REF] Kakar | Significance of intraepithelial lymphocytosis in small-bowel biopsy samples with normal mucosal architecture[END_REF][START_REF] Michaëlsson | Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin[END_REF] Of the 4 cases in our study where LD was attributed to immune dysregulation, all went through step 2 to ensure that both coeliac disease and gastrointestinal infections were excluded." -page 8, paragraph 3 35) Tables -In the line of "no causes found", one should also state the number of patients in whom increased IELs were self-limiting. Tables could be graphically improved. Aim: A prospective study of the aetiology of LD.

Method: One hundred patients with LD were rigorously investigated for coeliac disease and other known associations for LD by initial investigations of coeliac serology, and exclusion of infection. Of 34 with no explanation for LD, 29 underwent repeat duodenal biopsies following a gluten challenge.

Results: Coeliac disease was present in 16% of patients with LD. In the absence of a positive coeliac diagnosis, LD was most commonly associated with drugs (21%), infection (19%), immune dysregulation (4%), inflammatory bowel disease (2%), microscopic colitis (2%), sarcoidosis (1%) and IgA deficiency (1%). Of 34 with no known associations, 18/34 had symptoms of irritable bowel syndrome (IBS) and in 29/34 patients investigated with repeat duodenal biopsies the IEL count returned to normal in 22.

Conclusions: In 66% of cases of LD, a known association can be found by further investigations; importantly 16% will have coeliac disease. In those with no apparent cause, there may be an association with IBS and the IEL count became normal on repeat biopsy in 76%. surveillance and activation, with levels increasing in response to antigenic stress. [START_REF] Ferguson | Intraepithelial lymphocytes of the small intestine[END_REF][START_REF] Cerf-Bensussan | Gut intraepithelial lymphocytes and gastrointestinal diseases[END_REF] The normal IEL count was initially established in 1971 to be < 40 IELs per 100 enterocytes. This figure was determined from jejunal biopsies using a Crosby or Watson capsule, with counts being performed on 7µm thick sections. [START_REF] Ferguson | Quantitation of intraepithelial lymphocytes in human jejunum[END_REF] However, more recently the normal IEL count has been revised to < 25 IELs per 100 enterocytes. This is through duodenal biopsies being obtained endoscopically with histology performed on sections cut at 3-4 µm. [START_REF] Hayat | Quantitation of intraepithelial lymphocytes in human duodenum: what is normal?[END_REF][START_REF] Veress | Duodenal intraepithelial lymphocyte-count revisited[END_REF] Lymphocytic duodenosis (LD) is now defined by normal villous architecture and > 25 IELs per 100 enterocytes. [START_REF] Hayat | Quantitation of intraepithelial lymphocytes in human duodenum: what is normal?[END_REF][START_REF] Walker | Detection of celiac disease and lymphocytic enteropathy by parallel serology and histopathology in a populationbased study[END_REF] Some investigators may call this Marsh grade 1 (if suspicious of coeliac disease). LD is found in approximately 2% -3.8% of duodenal biopsies. [START_REF] Walker | Detection of celiac disease and lymphocytic enteropathy by parallel serology and histopathology in a populationbased study[END_REF][START_REF] Mahadeva | Is a raised intraepithelial lymphocyte count with normal duodenal villous architecture clinically relevant?[END_REF][START_REF] Hopper | What is the role of serologic testing in coeliac disease? A prospective, biopsy-confirmed study with economic analysis[END_REF] A few retrospective studies have identified the causes of LD which include coeliac disease, 9,10 gastrointestinal infections, [START_REF] Riordan | Small intestinal mucosal immunity and morphometry in luminal overgrowth of indigenous gut flora[END_REF][START_REF] Montgomery | The cell population of the upper jejunal mucosa in tropical sprue and postinfective malabsorption[END_REF] immunological disorders, [START_REF] Kakar | Significance of intraepithelial lymphocytosis in small-bowel biopsy samples with normal mucosal architecture[END_REF][START_REF] Michaëlsson | Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin[END_REF] non-steroidal anti-inflammatory drugs (NSAIDs), [START_REF] Kakar | Significance of intraepithelial lymphocytosis in small-bowel biopsy samples with normal mucosal architecture[END_REF][START_REF] Brown | Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa: an increasing diagnostic problem with a wide differential diagnosis[END_REF] inflammatory bowel disease (IBD), [START_REF] Tobin | Upper gastrointestinal mucosal disease in pediatric Crohn disease and ulcerative colitis: a blinded, controlled study[END_REF] IgA deficiency [START_REF] Klemola | Immunohistochemical findings in the intestine of IgA deficient persons: number of intraepithelial T lymphocytes is increased[END_REF] and more recently H.pylori. [START_REF] Memeo | Duodenal intraepithelial lymphocytosis with normal villous architecture: common occurrence in H. pylori gastritis[END_REF][START_REF] Nahon | Duodenal intraepithelial lymphocytosis during Helicobacter pylori infection is reduced by antibiotic treatment[END_REF] Vande Voort et al undertook a retrospective review of 124 patients with LD. [START_REF] Voort | Lymphocytic duodenosis and the spectrum of coeliac disease[END_REF] The investigators described features which would help to discriminate patients with LD who had underlying coeliac disease from those who did not, for example the presence or absence of HLA DQ2 or DQ8. However, they did not systematically investigate these patients for other causes of LD.

Over the last decade studies have focused mainly on evaluating patients with LD that belong to the spectrum of coeliac disease. Recognition of coeliac disease, even at this early stage is important, as these patients may have already developed symptoms and 4 complications, such as anaemia and osteoporosis, which can improve on a gluten-free diet (GFD). [START_REF] Kaukinen | Coeliac disease without villous atrophy. Revision of criteria called for[END_REF] Equally, excluding coeliac disease will prevent inappropriate prescription of a potentially expensive and socially inhibiting GFD, and instead allows recognition and treatment of any other underlying cause.

Methods of identifying those patients with LD that belong to the spectrum of coeliac disease include revisiting the patient's history and investigations as well as demonstrating histological deterioration on gluten. Enquiring specifically in the history about autoimmune disorders, such as Graves disease, is important due to the association with coeliac disease. [START_REF] Boelaert | Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease[END_REF][START_REF] Cosnes | Incidence of autoimmune diseases in coeliac disease: protective effect of the gluten-free diet[END_REF] However, conditions such as thyroid disease, rheumatoid arthritis, psoriasis and connective tissue disorders can cause raised duodenal IEL counts independently through a process of immune dysregulation [START_REF] Kakar | Significance of intraepithelial lymphocytosis in small-bowel biopsy samples with normal mucosal architecture[END_REF][START_REF] Michaëlsson | Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin[END_REF] this could be viewed as a speculative opinion and further work is required to delineate this relationship. Also dermatitis herpetiformis (DH), an itchy blistering rash, is almost always associated with coeliac disease, [START_REF] Fry | Dermatitis herpetiformis[END_REF] with up to 50% of patients demonstrating only subtle mucosal changes on duodenal biopsy. [START_REF] Fry | The small intestine in dermatitis herpetiformis[END_REF][START_REF] Fry | Lymphocytic infiltration of epithelium in diagnosis of gluten-sensitive enteropathy[END_REF] Finally, in first degree relatives of those with coeliac disease the risk of developing gluten-sensitive enteropathy is 5-10%. [START_REF] Murray | Coeliac disease in patients with an affected member, type 1 diabetes, iron-deficiency, or osteoporosis?[END_REF][START_REF] Fasano | Prevalence of coeliac disease in at-risk and not-at-risk groups in the United States: a large multicenter study[END_REF] Investigations to support the diagnosis of coeliac disease should involve testing for tissue transglutaminase antibody (tTG) and/or endomysial antibody (EMA) in the presence of a normal IgA level. [START_REF]Coeliac disease: recognition and assessment of coeliac disease[END_REF] However, patients with LD with possible/potential coeliac disease may present with a negative EMA, as the prevalence of a positive EMA strongly correlates with the severity of mucosal damage. [START_REF] Tursi | Low prevalence of antigliadin and antiendomysium antibodies in subclinical/silent coeliac disease[END_REF] For cases where the diagnosis is uncertain (such as in patients with LD) there may be a role for human leucocyte antigen (HLA) typing [START_REF]Coeliac disease: recognition and assessment of coeliac disease[END_REF] -HLA DQ2 or DQ8 are closely linked with coeliac disease, occurring in up to 98% of cases, [START_REF] Sollid | Evidence for a primary association of coeliac disease to a particular HLA-DQ alpha/beta heterodimer[END_REF] but they are also present in 25% of the normal population. [START_REF] Murdock | Diagnostic criteria for coeliac disease: time for change?[END_REF] An absence of these haplotypes can therefore be used as a negative predictive test. Approximately 50% of patients with LD have been shown to be negative for HLA DQ2 or DQ8, thus not belonging to the spectrum of coeliac disease. [START_REF] Voort | Lymphocytic duodenosis and the spectrum of coeliac disease[END_REF] HLA typing is expensive and should be reserved for equivocal cases. If the serology is negative and you still strongly suspect coeliac disease HLA typing can help, but it is not a first line investigation.

A recent Finnish study has shown that patients with LD who have both a positive EMA and HLA to belong to the spectrum of coeliac disease. The investigators randomised these patients to either a gluten containing diet (n 10) or GFD (n 13), and found progressive clinical, biochemical and histological deterioration in all those randomised to a gluten containing diet. Furthermore these individuals improved all parameters when they were commenced on a GFD, after the initial study period. [START_REF] Kurppa | Diagnosing mild enteropathy coeliac disease: a randomized, controlled clinical study[END_REF] A gluten challenge can also be useful in causing further mucosal deterioration in those patients with potential coeliac disease in whom the initial small intestinal biopsies reveal only minor abnormalities. [START_REF] Wahab | Gluten challenge in borderline glutensensitive enteropathy[END_REF] However, an initial trial response to a GFD is not as helpful, as up to 38% of patients with LD who have had a favourable response to a GFD are negative for the DQ2 or DQ8 haplotypes. [START_REF] Voort | Lymphocytic duodenosis and the spectrum of coeliac disease[END_REF] Despite the numerous possible causes of LD it has been noted by other investigators that patients may be given a diagnosis of coeliac disease solely on the presence of duodenal intraepithelial lymphocytosis. [START_REF] Biagi | The prevalence and the causes of minimal intestinal lesions in patients complaining of symptoms suggestive of enteropathy: a follow-up study[END_REF] For these reasons the aim of our study was to develop a systematic approach to diagnose the underlying causes of LD and treat patients effectively. Patients then underwent a 2-step process aiming to identify the underlying cause of their LD. Step 1 involved revisiting the patient's history and investigations for diagnostic clues (figure 1). In those where no cause was apparent/unclear or where coeliac disease was a possibility (including any patient with a positive HLA), patients then proceeded to step 2 (figure 1). This involved a six week gluten challenge followed by repeat coeliac serology, duodenal biopsies and small bowel aspirate for microscopy, culture and sensitivity. If no previous H.pylori status was documented then patients were questioned for symptoms at the time of their second biopsy and a CLO test was also performed.

A diagnosis of coeliac disease was made in those with positive serology (EMA or tTG), relevant symptoms and a HLA pattern of DQ2 or DQ8. These patients also had to have either progression of their LD to villous atrophy or a persistence of their LD.

Finally, in these individuals we also ensured that they had a symptomatic response to the GFD. Statistical analyses of data were performed using SPSS. Differences between the groups were assessed using Fisher's Exact Test.

Results

Of the 100 patients investigated 74 were women. The age range was from 16 to 83, with a median age of 47. The mean period of follow up was 18 months (range 2-72).

In order to find an underlying cause, 88/100 patients had to be investigated using the two-step approach. In these 100 patients, an underlying cause for LD was found in 66%, principally drug related (21%), coeliac disease (16%) and H. Pylori (14%).

There were 5 cases of gastrointestinal infection: giardia, threadworms, campylobacter and two cases of small bowel bacterial overgrowth. There were 4 cases of autoimmune disease including systemic sclerosis, hypothyroidism, rheumatoid arthritis and primary biliary cirrhosis. There was one case of sarcoidosis. There were 2 cases of inflammatory bowel disease. Ulcerative colitis was diagnosed on the basis of colonic biopsies which revealed mucosal inflammation and Crohn's was based on the second duodenal biopsy revealing granulomatous changes. Detailed causes of LD are shown in figure 2.

All cases of coeliac disease were positive for HLA DQ2 or DQ8, whereas 47/84 noncoeliac cases carried the DQ2 or DQ8 haplotypes, (p = 0.0004).

Despite an extensive work up, in 34 cases we were unable to identify a cause for the LD. Of these, 29/34 patients were willing to undergo re-biopsy. In 22/29 the IEL count was reduced to < 25 per 100 enterocytes on the second biopsy, whilst 7 had a persistently raised count with no apparent cause. When questioning these 34 patients, 18 had gastrointestinal symptoms consistent with a diagnosis of irritable bowel syndrome (IBS) using the ROME II Criteria. In 66% of cases an identifiable cause was found with drugs (NSAIDs or acetylsalicylic acid [ASA]), coeliac disease and H.pylori being the three most common causes. We are aware that a possible limitation of this study is that despite there being evidence supporting ASA induced small bowel injury, there is no specific data regarding ASA and raised IELs. Nevertheless, a recent study administrating low dose ASA over a short time period noted its use to be associated with increased occurrence of small intestinal mucosal damage. [START_REF] Smecuol | Low-dose aspirin affects the small bowel mucosa: results of a pilot study with a multidimensional assessment[END_REF] This was determined with the use of video-capsule endoscopy, faecal calprotectin and intestinal permeability testing.

These findings therefore suggest that ASA can induce small bowel inflammation and enteropathy and are supportive of our own observations. The concept of immune dysregulation causing LD has previously been noted and is poorly understood, possibly even speculative. [START_REF] Kakar | Significance of intraepithelial lymphocytosis in small-bowel biopsy samples with normal mucosal architecture[END_REF][START_REF] Michaëlsson | Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin[END_REF] Of the 4 cases in our study where LD was attributed to immune dysregulation, all went through step 2 to ensure that both coeliac disease and gastrointestinal infections were excluded.

In 34% of cases a cause for LD was not found. However, the majority of these patients normalised their IEL counts on the 2 nd set of duodenal biopsies. We speculate that this could be a post-infective picture (+/-IBS) and clinically would suggest reassurance in this group. In those with persistent LD the long term outcome is not yet clear and these patients remain under active follow-up. More than a half of the "no cause" found group had symptoms consistent with a diagnosis of IBS. The significance and association of IELs and IBS is contentious. Studies have shown conflicting data, with reported IEL counts ranging from normal to slightly elevated. [START_REF] Gargala | Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia[END_REF] [START_REF] Barbara | Postinfectious irritable bowel syndrome[END_REF] Suggested hypotheses include intraepithelial lymphocytosis being a marker of a luminal factor that triggers a low grade inflammatory response or an immunological memory that persists after earlier antigenic provocations. [START_REF] Törnblom | Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome[END_REF] It has been postulated that these cells may play a role in releasing mediators that evoke enteric nervous system responses, excite sensory afferent pathways, and induce visceral hyperalgesia. [START_REF] Barbara | Postinfectious irritable bowel syndrome[END_REF] In conclusion, in 66% of cases of LD, a known association can be found by further investigations; importantly 16% will have coeliac disease. HLA typing may have a role in differentiating between coeliac and non-coeliac cases. [START_REF]Coeliac disease: recognition and assessment of coeliac disease[END_REF] In those with no apparent cause, there may be an association with IBS and the IEL count became normal on repeat biopsy in 76%. Step 2

  prospective study of the aetiology of lymphocytic duodenosis.

  role of IELs in a clear manner. -We have now defined this according to the previous reviewer 1 suggestions. Comment 5 -"Lymphocytic duodenosis (LD) is defined by normal villous architecture and > 25 IELs per 100 enterocytes.

  mentioned some aspect of this in the discussion: (page 8 discussion last 3 lines of the page)

32 )

 32 How long was the follow-up of the patients without a specific cause (endoscopically and/ or clinically)? Had the initially increased IELs already normalized after the six-weeks glutenchallenge?Comment 32: 22 of the patients had a normal IEL count after the gluten challenge. The patients without a cause found who have still not normalised their IEL counts (n=7) are under active follow up. The long term outcome is not yet known.

Comment 35 :

 35 We have addressed the graphical images. Please see figures 1 & 2. In figure2we have added that 22/29 (76%) normalised their IEL counts on repeat biopsy All changes in the manuscript have also been highlighted in red duodenosis (LD) is defined by normal villous architecture and intraepithelial lymphocytes (IELs) > 25 per 100 enterocytes. Such patients should not be diagnosed with coeliac disease, solely by histology, as previous retrospective studies have suggested other associations with LD.

Introduction

  Duodenal intraepithelial lymphocytes (IELs) are involved in intestinal immune

Methods

  The study was conducted between the periods February 2003 to February 2010 at the Royal Hallamshire Hospital in Sheffield, a tertiary care centre for gastroenterology.One hundred patients with LD (> 25 IELs per 100 enterocytes) were sequentially identified and investigated to determine a cause for their raised IELs. All patients that were identified agreed to participate. The study was registered with both South Sheffield local ethics and audit committees.

34

 34

Discussion

  This is the first study to date investigating the causes of LD in a prospective and systematic manner.

10 Figure 1

 101 Figure 1: 2-step algorithm investigating patients with LD

  [START_REF] Hayat | Quantitation of intraepithelial lymphocytes in human duodenum: what is normal?[END_REF][START_REF] Walker | Detection of celiac disease and lymphocytic enteropathy by parallel serology and histopathology in a populationbased study[END_REF] Some investigators may call this Marsh grade 1 (if suspicious of coeliac disease). LD is found in approximately 2% -3.8% of duodenal biopsies. 6-8 Page 3, paragraph 3 6 The revised IEL counts are also better defined in these references, and Corazza's classification of coeliac disease supersedes Marsh by incorporating the concept of 25 IELs -J. Clin. Pathol. 2005; 58; 573-574, recent work confirms this in a population study, Gastroenterology. 2010; 139:112-9 Comment 6-We have now incorporated both Corazza's quoted 25/100 using the same reference as ours (ref 4) and added in the new gastroenterology reference (2%-3.8% of duodenal biopsies (ref 6-Gastroenterology. 2010; 139:112-9). 7.Retrospective studies:124 patients Vande Voort JL, Murray JA, Lahr BD et al. Lymphocytic duodenosis and the spectrum of celiac disease. Am. J. Gastroenterol. 2009; 104:142-8 -this study looked at 124 patient. Comment 7 -We have now addressed this in the text accordingly. "Vande Voort et al undertook a retrospective review of 124 patients with LD.

  -

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	e r
	R
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	v i e
	w
	9

Causes of LD Causes of lymphocytic duodenosis (n 100)

	35 Figure 2: 34 40
						Revisit history & recent investigations
		30				No cause found * 1) Autoimmune disorders, DH, family history, medication -i.e NSAIDs, aspirin (acetylsalicylic acid [ASA]) Drugs (NSAIDs 13, ASA 8)
		25				Coeliac disease
			21			2) Bloods -coeliac serology (EMA, tTG), immunoglobulins, HLA typing H.Pylori
	%	20				3) Stool culture results	GI infection
		5 10 15	F o r 16 14 F o r F o r F o r F o r	5	4	4) Colonoscopy (if indicated) with colonic / terminal ileal biopsy results 5) H.pylori status -13 C Urea breath test or CLO test Immune dysregulation 2 2 1 1 IBD Microscopic colitis Sarcoidosis IgA deficiency
	P e P P P P Causes e e e e Coeliac suspicion (inc. + ve HLA) or 0 no clear cause e r * 22/29 (76%) of this group normalised their IEL counts on repeat biopsy clear (non-coeliac) diagnosis made inc. negative HLA & coeliac serology, no history suspicious of coeliac disease e r e r e r e r
					R R R R R
					Investigations at time of endoscopy e e e e e
			Repeat OGD and coeliac serology (EMA/tTG) after a 6 week gluten challenge (10g/day = 4 slices of bread/day)	4 x duodenal biopsies Small bowel aspirate for microscopy, culture & sensitivity v i e v i e v i e v i e v i e CLO test (if no recent H.pylori result) w w w w w
	Coeliac disease, other cause, normal
	repeat biopsy or persisting
			unexplained IELs
						11

Alimentary Pharmacology & Therapeutic

Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK.

Histocompatability & Immunogenetics, NHS Blood & Transplant, Sheffield, UK. Corresponding author and reprint requests: Dr Imran Aziz, Department of Gastroenterology and Liver unit, Room P39, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK.e-mail: imran.aziz@sth.nhs.uk

Acknowledgments: We wish to acknowledge the help of Professor TJ Stephenson, Dr SS Cross and Dr A Dube (Department of GI Histopathology, Royal Hallamshire Hospital, UK) who were all involved in the reporting and review of these cases.

Disclosures: none

Funding: none

Conflict of interests: none

Key words: lymphocytic duodenosis; duodenal intraepithelial lymphocytes; coeliac disease; irritable bowel syndrome; H.pylori Guarantor of the article: Dr Imran Aziz Contributors: IA helped design the study; recruit patients; collect, analyse and interpret data; and draft the article. KEE and ADH helped recruit patients; collect, analyse, interpret data; and review the final version of the manuscript. DMS helped collect data and review the final version of the manuscript. DSS conceived and designed the study; helped recruit patients; collect, analyse and interpret data; and review the final version of the manuscript.