Pathogenic antibody recognition of cartilage |
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Authors: | Kutty Selva Nandakumar |
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Institution: | (1) Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden |
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Abstract: | Antibodies against cartilage proteins are highly prevalent in the sera and synovial fluids of rheumatoid arthritis (RA) patients
and also precede disease induction in various spontaneous and induced animal models of arthritis. These antibodies play an
important role in the induction and perpetuation of the clinical disease. Antibodies binding to cartilage protein(s), especially
the major articular cartilage protein, collagen type II (CII) can induce, in naive mice, an acute form of arthritis that can
substantially destroy the cartilage and bone architecture. More importantly, these anti-CII antibodies can also directly cause
the destruction of the target tissue preceding and independently of disease development and in the absence of any other pathogenic
inflammatory factors or the action of immune cells. Alternatively, antibodies to citrullinated protein antigens and rheumatoid
factor are well-validated prognostic and diagnostic markers of severe erosive RA, although their arthritogenic potential is
questioned. Recently, we have found that the monoclonal antibodies to citrulline-modified cartilage protein can bind cartilage
and synovial tissue and mediate arthritis in mice. Similarly, one of the pathogenic anti-CII monoclonal antibodies has rheumatoid-factor-like
activity, suggesting a disease-inducing role for these commonly prevalent antibodies in RA patients. Interestingly, recent
findings have also shown that the enzymatic cleavage or modification of pathogenic IgG antibodies protects the cartilage surface,
thereby opening up new therapeutic possibilities for protecting the cartilage from inflammatory damage. |
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