Genetic architecture underlying IgG-RF production is distinct from that of IgM-RF.

This article focuses on the genetic associations of IgG rheumatoid factor (IgG-RF) subfractions in rheumatoid arthritis (RA), particularly in relation to HLA-DRB1 alleles and shared epitope (SE) alleles. Analyzing 743 RA patients and 2008 healthy controls, the study found that both IgG-RF positive and negative RA subsets showed comparable associations with SE alleles; however, the IgG-RF(–) subset was uniquely associated with HLA-DRB1*04:01, an SE allele more common in Europeans than in the Japanese population. These associations were independent of anti-citrullinated protein antibody (ACPA) status, suggesting distinct genetic architectures underlying RA autoantibody profiles. The findings highlight potential genetic heterogeneity within RA subgroups, which may inform future research on RA pathogenesis and clinical management.