In vitro stimulation of C1s proteolytic activities by C1s-presenting autoantibodies from patients with systemic lupus erythematosus.
Anti-C1s autoantibodies (IgG forms), which recognize the conjunction of C1s heavy chain and light chain (C1s-presenting autoantibodies) from patients with systemic lupus erythematosus (SLE), have been found to stimulate C1s enzymatic activities. This is due to acceleration of the proteolytic hydrolysis of the synthetic substrate C1-1 by C1s, enhancement of the complex formation of C1s with its natural pseudosubstrate, C1 inhibitor (C1 inh), and promotion of proteolytic activation of its natural substrate, C4. Seven of fifteen samples from patients with SLE were found to contain such autoantibodies. The hydrolysis of the synthetic substrate C1-1 catalyzed by C1s in 25 to 27 min in the presence of anti-C1s autoantibodies was equivalent to the hydrolysis of C1-1 catalyzed by C1s alone or C1s with control IgG from healthy sera in 110 min, approximately fourfold faster than the reaction in the absence of anti-C1s autoantibodies. Densitometry scanning data showed that the formation of the C1s-C1 inh complex in the presence of anti-C1s autoantibodies was three to four times greater than that with control IgG. It was also noticed that the autoantibodies convert almost all of the latent forms of C1s to an active form that binds to C1 inh. Another group of Western blots showed that C1s cleaved C4 alpha-chain three times faster in the presence of autoantibodies than of control IgG. It is likely that the overconsumption of complement components is common in the pathogenesis of tissue damage occurring in SLE.
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Department of Medicine, School of Medicine, Queen Elizabeth Hospital, University of Birmingham, Edgbaston, United Kingdom. hes@novell5.bham.ac.uk
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D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000494:pharmacology*; D003173:Complement C1s / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D003181:Complement C4 / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000276:immunology; D004789:Enzyme Activation; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D003181:Complement C4; D003169:Complement Inactivator Proteins; D007074:Immunoglobulin G; D003173:Complement C1s