Immunoglobulin allotypes in rheumatoid arthritis

The HLA region of chromosome 6 may account for as little as 20% of the genetic contribution to rheumatoid arthritis (RA). Previous studies have shown associations with immunoglobulin heavy chain allotypes (Gm) coded for by genes on chromosome 14. We review evidence that G1m(x)-bearing haplotypes are associated with DR4-positive, but not DR4-negative RA. A differing Gm association has been reported in two studies of RA patients with circulating antibodies to native type II collagen, which might constitute a specific genetic subgroup. A family study has shown no evidence for genetic linkage between Gm allotypes and susceptibility to RA. It is possible that Gm (or linked 14th chromosomal genes) may influence susceptibility to RA by interacting with different genes within the HLA region. Immunoglobulin light chain allotypes (Km) coded by genes on chromosome 2 show no consistent association with RA.