the systemic lupus erythematosus sle disease autoantigencalreticulin can inhibit c1q association with immune complexes following its release from cells during infection and inflammation calreticulin crt can act as an autoantigen in diseases such as sle why crt is a target of protective immunity and whether it may interfere with innate immunity once released from cells during inflammation is unclear in the present study we found that crt was detected more frequently in sle sera and in higher amounts than found in control sera approximately 40 of sle sera tested contained autoantibodies against crt as detected by elisa and immunoblotting crt was found to be predominantly in the sera of sle patients associated with immune complexes and c1q and only bound to the surfaces of neutrophils in the presence of low levels of calcium and magnesium in order to further investigate the c1qcrt interaction recombinant crt and its discrete domains n p and cdomains were produced in escherichia coli crt binds to globular head region of c1q primarily via its n and pdomains the ndomain was shown to be the most autoantigenic region of crt as the anticrt autoantibodies from most patients reacted against this region crt also altered c1qmediated immune functions the pdomain of crt bound to c1q and reduced the binding of immune complexes in sle sera to immobilized c1q full length crt and its n and pdomains were able to reduce the c1qdependent binding of immune complexes to neutrophils and solidphase bound c1q we conclude that crt once released from leucocytes during inflammation may not only induce an antigenic reaction but also interfere with c1qmediated inflammatory processes