The function of I and i antigens are unknown but may be related to hematopoiesis, the production of blood. The rapid conversion from i to I antigens after birth suggests that I antigen plays an important role in adult red blood cells. The presence of the linear i antigen in fetuses, rather than the branched I antigen, may have developed as an evolutionary mechanism to prevent ABO hemolytic disease of the fetus and newborn. Enhanced expression of i antigen is associated with conditions involving stress hematopoiesis such as leukemia and sickle cell disease. Transient autoantibodies against I antigen are common, especially after infection by Mycoplasma pneumoniae, and are rarely significant except in cold agglutinin disease. Transient antibodies against i antigen are common after infectious mononucleosis and are also not clinically significant. Antibodies which recognize both I and i antigens are termed anti-j antibodies. Cold agglutinin disease The autoantibodies involved in cold agglutinin disease are usually against I antigen. The antibodies are usually IgM (kappa subtype), unlike transient autoantibodies which are generally IgG. Cold-reactive IgM antibodies (cold agglutinins) bind to I antigen on red blood cells, and unlike IgG, are able to cause agglutination of red blood cells and activate complement to cause hemolysis, leading to anemia. Adult i phenotype Rarely, individuals have the i antigen on their red blood cells into adulthood, known as the adult i phenotype. This is due to the presence of a mutation in the GCNT2 gene which encodes the I-branching enzyme. These individuals have alloantibodies against the I antigen, though these are typically cold agglutinins and are unlikely to cause transfusion reactions. The adult i phenotype is associated with congenital cataracts, most markedly in Japanese and Taiwanese people and least markedly in Caucasian people. Cataracts occur when i antigen rather than I antigen is present on the epithelium of the lens, due to a mutation in the form of the I-branching enzyme which is expressed in lens epithelium, IGNTB. The adult i phenotype is inherited in a recessive manner.
Ii antigen system
MNS antigen system
Yt antigen system
Kidd antigen system
Lewis antigen system
Duffy antigen system
Lutheran antigen system
Kell antigen system