Increase of duodenal and ileal mucosal cytotoxic lymphocytes in juvenile idiopathic arthritis.
Intestinal gamma/delta- intraepithelial lymphocytes (IEL) have increased in children with juvenile idiopathic arthritis (JIA). To further characterise intestinal immune activation in these children, we have quantitated cytotoxic lymphocytes in intestinal mucosa. We studied 23 children with JIA suffering from gastrointestinal symptoms with gastroduodenoscopy and colonoscopy. The control children (n=20) had GI-symptoms but eventually shown not to have any significant gastrointestinal disease. Granzyme A (GrA) and Granzyme B (GrB) expressing lymphocytes in the epithelium and lamina propria were counted in immunostained sections of ileal and duodenal biopsies. The number of GrB expressing IELs was increased in duodenal mucosa in patients with JIA. In the ileum the number of both GrB and GrA positive IELs was similarly increased. No significant differences in the counts of the lamina propria GrA or GrB expressing cells were observed. Granzyme expression was not associated with the duration or with the severity of the disease, or with medication. These observations suggest that lymphocyte cytotoxicity is abnormally increased in the intestinal mucosa in JIA. Since a similar pattern of activation has been seen in food allergy and celiac disease, we speculate that some luminal, possibly a nutritional factor may be involved in JIA as well. Further studies are needed to see whether cytotoxic activation plays any role in the pathogenesis of JIA.