INTERACTION OF HLA AND GM IN AUTOIMMUNE CHRONIC ACTIVE HEPATITIS

Abstract

An immunogenetic study of autoimmune chronic active hepatitis (CAH) showed the relative risk (RR) for this disease was 11.6 for patients who were HLA-B8, 11.7 for patients who were DR3, and 2.3 for patients who were Gma+x+. The Gm haplotype Gma+x+ was present in 18 of 40 (45%) patients with HLA-B8, but in none of 10 patients negative for HLA-B8; in 180 healthy controls Gma+x+ was evenly distributed among those positive (24%) and negative (18%) for HLA-B8. The RR was lowest in patients lacking HLA-B8 but positive for Gma+x+. Relative to this low-risk group, the risk was increased 39 times in subjects with both HLA-B8 and Gma+x+, 15 times in subjects with HLA-B8 who were not Gma+x+, and twice in subjects who were neither HLA-B8 nor Gma+x+. Statistical analysis indicated that the 3-factor effect (disease risk affected by non-additive effects of HLA-B8 and Gma+x+) was significant (P < 0.01), as were the main effects of HLA-B8 (P < 0.001) and Gma+x+ (P < 0.02). In the presence of HLA-B8, genes linked to Gma+x+, an Ig CH [H chain constant region] allotype, may contribute to the development of autoimmune chronic active hepatitis; in the absence of HLA-B8 these same genes appear to be inactive. This may indicate interactions between MHC [major histocompatibility complex] gene products and VH [H chain variable region] gene products in the presentation and recognition of autoantigen(s) in autoimmune hepatitis.