Specificity of IgM M-proteins in 77 patients with neuropathy associated with IgM monoclonal gammopathy

Susceptibility to myasthenia gravis (MG) is known to involve genes residing in the major histocompatibility complex class I and II regions (HLA-B8 and DR3). Immunoglobulin heavy chain constant region (IgCH) allotypes have also shown some associations with MG. We have used restriction fragment length polymorphism analysis with probes to the IgCH switch (S) regions μ and α1 and the downstream marker D14S1 to investigate 189 Caucasoid patients with well-defined MG. A highly significant increase in the frequency of the 2.6 kilobase (kb) Sμ homozygous genotype and the 2.6 kb Sμ allele was found in patients with disease onset after the age of 40 years (late onset) compared with normal controls (P<0.00075 and P<0.025 respectively). No association was found at the Sα1 or D14S1 loci. In patients with an associated thymoma there was a moderate increase in the frequency of the 2.6 kb Sμ and 7.4 kb Sα1 genotypes. These results independently support the previous separation of the late-onset subgroup. Finally, the stronger associations at Sμ rather than at the downstream Sαl, Gm and D14S1 loci suggest that the genes predisposing to MG are located within the variable region of the Ig heavy chain loci.