[Immunogenetics of myasthenia gravis. Significance of HLA-, complement and Cm gene systems for clinical and immunologic parameters].

In 82 non-related patients with myasthenia gravis the following immunogenetic marker systems were investigated: HLA-A, -B, -C, -DR antigens, complement polymorphisms for Bf, C3 and C4 as well as immunoglobulin allotypes G1m, G3m and Km. In 78 patients the level of circulating acetylcholin receptor autoantibody was measured. The HLA antigens showed no significant differences in frequency when compared with healthy controls. This was also true for the HLA-bound Bf and C4 polymorphism, the non-HLA-bound C3 polymorphism and the immunoglobulin allotypes. A significant (P less than 0.005) increase in heterozygote frequency of 39.7% in the Gm allotype combination G1m (1), (17); (3) when compared with an expected frequency as calculated from the gene frequency of 19.8% was found. HLA-B8 and/or HLA-DR3 positive myasthenia gravis patients showed a significantly (P less than 0.025 and less than 0.005) earlier average onset of the disease whereas in HLA-DR2 positive patients the average onset was later (P less than 0.05). The same HLA antigens correlated with quantitative differences in the acetylcholine receptor autoantibodies: HLA-B8 and/or -DR3 positive patients had on average higher antibody levels than HLA-B8 or -DR3-negative patients. The difference for HLA-DR3 was statistically significant (P less than 0.05). On the other hand patients with HLA-DR2 antigens had significantly lower antibody levels (P less than 0.025). Increased mean antibody levels were also seen in G1m(1), (17) allotype (P less than 0.005) and G3m(21) (P less than 0.05). As the HLA antigens and Gm allotype genes are situated on different chromosomes (C6 and C14) two distinct gene regions are identified in myasthenia gravis. These are associated with quantitative differences in acetylcholine receptor antibody titres.