AN INCREASED RISK OF CROHNS-DISEASE IN INDIVIDUALS WHO INHERIT CLASS-II DRB3(ASTERISK)0301 ALLELE

The role of inflammatory T cells in Crohn's disease suggests that inhe rited variations in major histocompatibility complex (MHC) class II ge nes may be of pathogenetic importance in inflammatory bowel disease, T he absence of consistent and strong associations with MHC class II gen es in Caucasian patients with inflammatory bowel disease probably refl ects the use of less precise typing approaches and the failure to type certain loci by any means, A PCR-sequence-specific oligonucleotide-ba sed approach was used to type individual alleles of the HLA class II D RB1, DRB3, DRB4, and DRB5 loci in 40 patients with ulcerative colitis, 42 Crohn's disease patients, and 93 ethnically matched healthy contro ls, Detailed molecular typing of the above alleles has previously not been reported in patients with inflammatory bowel disease, A highly si gnificant positive association with the HLA-DRB30301 allele was obser ved in patients with Crohn's disease (P = 0.0004) but not in patients with ulcerative colitis, The relative risk for this association was 7. 04, Other less significant HLA class II associations were also noted i n patients with Crohn's disease. One of these associations involved th e HLA-DRB11302 allele, which is known to be in linkage disequilibrium with HLA-DRB30301. These data suggest that a single allele of an inf requently typed HLA class II locus is strongly associated with Crohn's disease and that MHC class II molecules may be important in its patho genesis.