C1q inhibits autoantibody binding to calreticulin.
Calreticulin (CR) is a new rheumatic disease-associated autoantigen that is intimately associated with the Ro/SS-A ribonucleoprotein. CR autoantibodies are frequently observed in patients with photosensitive forms of lupus erythematosus (LE). CR has been shown to be highly homologous to cC1q-R, the cell surface receptor that binds the collagenous domain of the first component of complement, C1q. C1q has also been shown to directly bind to CR. We therefore asked whether the binding of C1q to CR might interfere with the binding of CR autoantibody to CR. Full-length recombinant human CR, an E. coli fusion proteins was used as antigen in a direct enzyme-linked immunosorbent assay (ELISA). CR autoantibody-containing sera were assayed before and after C1q removal by two different methods: by heating sera at 56 degrees C for 30 min or adding monoclonal anti-C1q antibodies. ELISA optical density (OD) values were found to be consistently higher in sera depleted of C1q by both methods compared to unmodified sera. The addition of purified C1q to C1q-depleted sera resulted in ELISA OD values similar to those of unmodified sera. These results suggest that C1q levels present in human serum can inhibit the binding of CR autoantibody to CR. One can speculate that the failure of C1q to mask CR autoepitopes in individuals with genetic deficiency of C1q could contribute to the high rate of photosensitive LE that occurs in such individuals.
Department of Dermatology, UT Southwestern Medical Center, Dallas, Texas, USA.
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Racila
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Sontheimer
D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000276:immunology* / Q000378:metabolism*; D037282:Calreticulin; D015922:Complement C1q / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D010787:Photosensitivity Disorders / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D020733:RNA, Small Cytoplasmic; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D012261:Ribonucleoproteins / Q000032:analysis / Q000276:immunology* / Q000378:metabolism*; D000099207:SS-A Antigen
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D015922:Complement C1q; D020733:RNA, Small Cytoplasmic; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human