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Recombinant human C1q is a biotechnologically produced version of the C1q protein, the recognition component of the classical complement pathway. It is a large, complex glycoprotein consisting of 18 polypeptide chains (six each of A, B, and C chains). In physiological conditions, C1q binds to the Fc regions of IgM or IgG in immune complexes, or directly to pathogens and apoptotic cells, to initiate the complement cascade. However, research in rheumatoid arthritis (RA) has identified a pathogenic role for C1q; it can bind to the C1q-binding protein (C1QBP) on synovial macrophages, inducing a SARM1-dependent metabolic crisis characterized by NAD+ depletion, ATP loss, and PANoptotic cell death. This mechanism drives chronic tissue inflammation rather than resolution. While recombinant human C1q is a vital research tool for studying complement-mediated signaling and is a theoretical candidate for enzyme replacement therapy in rare cases of hereditary C1q deficiency, it is not currently an approved pharmaceutical product.
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