HLA-DRB1 genes and extraarticular rheumatoid arthritis

Rheumatoid arthritis (RA), a systemic autoimmune condition, causes joint damage and sometimes extraarticular lesions (cutaneous vasculitis, neuropathy, Felty's syndrome, pericarditis, intersticial lung disease) that may be life threatening. The reason why extraarticular features will develop in rare RA patients is unknown.In a previous issue of Arthritis Research and Therapy, Turesson and colleagues [1] analyse the influence of HLA-DR genes on the development of extraarticular RA in a series of 159 patients with extraarticular RA matched with 178 patients with purely articular RA.HLA-DR genes are the principal genetic factor contributing to RA. HLA-DR alleles DRB1*0401, *0404, *0405 (serologically HLA-DR4), DRB1*0101,*0102 (HLA-DR1) and HLA-DRB1*1001 (HLA-DR10) are associated with RA [2]. HLA-DR genotypes (the two HLA-DRB1 genes expressed by any individual) determine the risk to develop RA. 'Double dose' genotypes such as DRB1*0401/DRB1*0404 carry very high risks to develop RA (it is very difficult to find healthy, RA free controls with the DRB1*0401/0404 genotype), whereas 'single dose' genotypes such as DRB1*0401/DR7 carry more limited risks [3].The Turesson study includes patients with extraarticular RA defined by cutaneous vasculitis, neuropathy, Felty's syndrome, intersticial lung disease, pericarditis, pleuritis, scleritis, episcleritis and glomerulonephritis. It asks questions about HLA-DR alleles and HLA-DR genotypes and their association with extraarticular RA as a whole or with particular items included in extraarticular RA.Its main findings are that shared epitope positive HLA-DR4 alleles (in this population, mostly HLA-DRB1*0401 and HLA-DRB1*0404) are associated with extraarticular RA globally, but that neither DRB1*0401 nor DRB1*0404 is associated with any particular clinical feature, except for HLA-DRB1*0401, which is associated with Felty's syndrome. When considering the influence of DRB1 genotypes, the findings are very similar. Genotypes containing