C1q in autoimmune diseases: rheumatoid arthritis.
Rheumatoid arthritis is an autoimmune disease involving stimulation of T cells and the production of autoantibodies. In this disease autoantibodies to collagen type II are believed to play a major role in inflammatory events ultimately resulting in joint destruction. However, collagen type II-containing cartilage has been discussed as one of the primary antigens (as evidenced by animal models), despite not being accessible. Evidence is presented here for the involvement of C1q, the collagen-like subunit of the first component of complement, in the pathogenesis of rheumatoid arthritis. The C1q A-chain contains an epitope exhibiting an identical sequence to part of an arthritis modulating epitope from collagen type II. Furthermore, preapplication of a synthetic peptide, representing the epitope on the C1q A-chain, has been shown to delay the onset and reduce the severity of collagen-induced arthritis in a DBA/1 mouse model. Since the complement system, in particular C1q (as part of the first component of the classical pathway), plays a major role in the inflammatory process, we propose that the collagen-like C1q molecule, altered during the inflammatory process, may result in the generation of autoantibodies which also recognize collagen type II, and may thus be considered as a link between the early inflammatory process in the joint and the only later occurring cartilage destruction.
Maeurer
M J
MJ
Institute of Medical Microbiology, Johannes Gutenberg University, Hochhaus am Augustusplatz, Mainz, Germany.
Trinder
P K
PK
Störkel
S
S
Loos
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology*; D015922:Complement C1q / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000473:pathology
D007136:Immunoglobulins; D015922:Complement C1q