Collagen antibodies in rheumatoid arthritis. Significance of antibodies to denatured collagen and their association with HLA-DR4

The frequency, specificity, and HLA associations of antibodies to collagen were examined in 54 patients with severe rheumatoid arthritis (RA) and in 67 control subjects, using native and denatured bovine type II collagen as reactants in a solid-phase radioimmunoassay. Reactivity to denatured collagen was significantly higher in the RA patients than in the controls (P = 0.004). Reactivity to native collagen was substantially lower than reactivity to denatured collagen and was similar in RA patients and controls. DR4 positive RA patients had significantly greater reactivity to denatured collagen compared with DR4 negative RA patients (P = 0.03), but levels of antibody to native collagen were similar among DR4 positive and DR4 negative patients. These data lend support to the idea that denatured collagen is an important secondary reactant in immune-mediated perpetuation of RA.