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 autoantibodie s are frequently observed in patients with photosensitive forms of lupus er ythematosus (LE). CR has been shown to be highly homologous to cC1q-R, the cell surface receptor that binds the collagenous domain of the first compon ent 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 b inding of CR autoantibody to CR. Full-length recombinant human CR, an E. co li fusion proteins was used as antigen in a direct enzyme-linked immunosorb ent 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 b y both methods compared to unmodified sera. The addition of purified C1q to C1q-depleted sera resulted in ELISA OD values similar to those of unmodifi ed sera. These results suggest that C1q levels present in human serum can i nhibit the binding of CR autoantibody to CR. One can speculate that the fai lure of C1q to mash CR autoepitopes in individuals with genetic deficiency of C1q could contribute to the high rate of photosensitive LE that occurs i n such individuals.