ALTERED (OXIDIZED) C1Q INDUCES A RHEUMATOID ARTHRITIS-LIKE DESTRUCTIVE AND CHRONIC INFLAMMATION IN JOINT STRUCTURES IN ARTHRITIS-SUSCEPTIBLE RATS

Previous studies have identified an altered C1q molecule in synovial f luids from the joints of rheumatoid arthritis patients. We therefore i mmunized arthritis-susceptible Lewis 1A.AVN rats with either native C1 q (C1q nat), altered (oxidized) C1q (C1q ox), or type II collagen (CII , induces arthritis in these animals), in order to induce arthritis. U nlike C1q nat, both CII and C1q ox were able to induce swelling and er ythema of joints consistent with an arthritis-like inflammatory reacti on. Histopathological evaluation of individual joint sections revealed synovitis, bursitis and tendovaginitis, massive joint destruction, an d severe pannus formation. In a time-course study, no differences in o nset of arthritis or pathology were observed between C1q ox-induced ar thritis and that induced by CII. High titers of antibodies recognizing CII, but not Clq (native or oxidized), were detected in rats immunize d with CII. In contrast Clq ox, but not Clq nat, induced antibodies re active with both Clq and CII. Antibodies from C1q ox-immunized animals contained an antibody subset that reacted with C1q but not CH and a s ubset that reacted with CII but not C1q, implying that induction of an immune response to CH does not require CII. These data support the hy pothesis that C1q may provide one of the early antigens involved in in duction of arthritis, before CII becomes available as antigen. (C) 199 7 Academic Press.