Humoral autoreactivity directed against surfactant protein-A (SP-A) in rheumatoid arthritis synovial fluids

Abstract

SUMMARY SP-A is found principally in the lung, and has been associated with lamellar bodies also found in the synovial joint. Both SP-A and C1q contain collagen-like regions, and SP-A and C1q have some structural similarities, both having a globular head region and a collagen-like tail. Here we are able to show that (i) autoreactivity to SP-A, as expressed by IgG and IgM autoantibodies, is present in synovial fluid (SF) isolated from patients with rheumatoid arthritis (RA); (ii) in absorption experiments only a limited degree of cross-reactivity between autoantibodies reactive with C1q and SP-A is observed; (iii) there is no cross-reactivity between autoantibodies reactive with type II collagen (CII) and those reactive with SP-A or C1q; (iv) autoantibodies react with polymeric (dimers and larger) SP-A, but not with monomeric SP-A subunits, indicating that a degree of quaternary structure is required for antibody binding. Unlike CII, which not accessible in the normal joint, both SP-A and C1q are available within the SF in patients with RA and may therefore provide antigens driving an autoimmune response directed against collagen-like structures.