Interferon-gamma production in response to in vitro stimulation with collagen type II in rheumatoid arthritis is associated with HLA-DRB1*0401 and HLA-DQ8

Interferon-gamma was measured in supernatants after in vitro stimulation of peripheral blood mononuclear cells with collagen type II (CII), purified p rotein derivative or influenza virus. Interferon-gamma production in respon se to CII was similar in rheumatoid arthritis (RA) patients and healthy con trol individuals. The interferon-gamma response to purified protein derivat ive and influenza virus was lower in RA patients, reflecting a general T-ce ll hyporesponsiveness in RA. After recalculating the response to CII taking this hyporesponsiveness into account the CII response was higher in RA pat ients, and was associated with human leucocyte antigen (HLA)-DRB1*0401 and HLA-DQA1*0301-DQB1*0302 (HLA-DQ8). Rheumatoid arthritis patients with eleva ted serum levels of immunoglobulin (Ig)G anti-CII antibodies had lower CII- induced interferon-gamma production than patients with low anti-CII levels. The relative increase in CII-reactivity in RA patients as compared with he althy control individuals, and the association of a higher response with RA -associated HLA haplotypes, suggest the existence of a potentially pathogen ic cellular reactivity against CII in RA.