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 fluids from the joints of rheumatoid arthritis patients. We therefore immunized arthritis-susceptible Lewis 1A.AVN rats with either native C1q (C1q nat), altered (oxidized) C1q (C1q ox), or type II collagen (CII, induces arthritis in these animals), in order to induce arthritis. Unlike C1q nat, both CII and C1q ox were able to induce swelling and erythema of joints consistent with an arthritis-like inflammatory reaction. Histopathological evaluation of individual joint sections revealed synovitis, bursitis and tendovaginitis, massive joint destruction, and severe pannus formation. In a time-course study, no differences in onset of arthritis or pathology were observed between C1q ox-induced arthritis and that induced by CII. High titers of antibodies recognizing CII, but not C1q (native or oxidized), were detected in rats immunized with CII. In contrast C1q ox, but not C1q nat, induced antibodies reactive with both C1q and CII. Antibodies from C1q ox-immunized animals contained an antibody subset that reacted with C1q but not CII and a subset that reacted with CII but not C1q, implying that induction of an immune response to CII does not require CII. These data support the hypothesis that C1q may provide one of the early antigens involved in induction of arthritis, before CII becomes available as antigen.
Trinder
P K
PK
Institute of Medical Microbiology & Hygiene, Johannes Gutenberg University, Mainz, 55101, Germany.
Maeurer
M J
MJ
Stoerkel
S S
SS
Loos
M
M
D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D015922:Complement C1q / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D007596:Joints / Q000276:immunology / Q000473:pathology*; D010084:Oxidation-Reduction; D051381:Rats; D011917:Rats, Inbred Lew
D015922:Complement C1q