T-CELL RECEPTOR-GAMMA GENE POLYMORPHISMS AND CLASS-II HUMAN LYMPHOCYTE ANTIGEN GENOTYPES IN PATIENTS WITH CELIAC-DISEASE FROM THE WEST OF IRELAND

Although celiac disease has one of the strongest human lymphocyte anti gen (HLA) class II associations of any human illness, it is clear that at least one gene that is not linked to the HLA region also is requir ed for its pathogenesis. The occurrence of large numbers of gamma delt a T cells in the bowel mucosa of patients and the recent description o f T cell receptor (TCR) gamma chain polymorphic variants identified by restriction fragment length polymorphism analysis led the authors to examine TCR gamma genotypes in relation to HLA-DR, DQ genotypes in 89 patients with celiac disease and 55 control subjects from the West of Ireland. The overall frequency of TCR gamma genotypes in patients and control subjects was comparable. However, most of the patients had 1 o f 3 HLA-DR3 genotypes (DR3/15, 3/7, or 3/3), and there was a significa nt alteration of the expected frequency of TCR gamma genotypes among p atients with these three genotypes. The major differences were an incr eased association of HLA-DR3 homozygosity, with TCR gamma genotypes ha ving a 16.0 kb fragment and an increased frequency of DR3/7 heterozygo sity and decreased frequency of DR3/15 heterozygosity, respectively, i n association with the TCR gamma 13.0/11.3 kb genotype. Based on their results, there is the possibility that an interaction between the pro ducts of two polymorphic and unlinked gene regions contributes to the pathogenesis of celiac disease.