Immunoglobulin heavy chain constant region variants in rheumatoid arthritis

Abstract

Polymorphisms within the immunoglobulin heavy chain constant region at switch (S)μ and Sαl loci were studied in patients with rheumatoid arthritis (RA) and controls in parallel with Gm and A2m allotyping. SFμ and Sαl restriction fragment length polymorphisms were defined using a SFt probe which was hybridised to SstI digests of DNA extracted from circulating white cells. There were no differences in Sμ and Sα1 gene or phenotype frequencies between RA and control groups nor within the RA population between DR4 positive and negative subjects. The Gm allotype Glm(x), coded for by genes at the gamma-1 locus, was found in 29/92 (32%) of DR4 positive and 5/52 (10%) of DR4 negative subjects with RA, as compared with 25/115 (22%) cf controls. The A2m allotype A2m(2), coded for by the α2 locus, was found in 11/92 (12%) of DR4 positive subjects with RA, zero of 52 DR4 negative subjects, and 5/115 (4%/o) of controls. These results exclude a major effect of genes within the heavy chain constant region linked to μ or α1 loci on susceptibility to RA, but suggest that further study of variants closely linked to the α2 locus is indicated.