ANTI-C1Q RECEPTOR CALRETICULIN AUTOANTIBODIES IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE)/

SLE is a disease characterized by the presence of multiple autoantibod ies and high levels of circulating immune complexes. We studied the pr esence and functional relevance of autoantibodies directed against a r eceptor for the collagen-like stalks of the first subcomponent of comp lement, also known as calreticulin (cClqR/CaR), in patients with SLE. In a cross-sectional study it was found that higher titres of antibodi es against cClqR/CaR are present in sera of SLE patients compared with normal donors. No association between anti-cClqR/CaR titres and SLE d isease activity was found. Following gel filtration of SLE serum it wa s found that anti-cClqR/CaR reactivity is associated with the peak of monomeric IgG. Purified IgG from patients was able to specifically imm unoprecipitate cClqR/CaR. Since we have shown previously that cClqR/Ca R is able to inhibit the haemolytic activity of Clq, we determined a p ossible pathogenic role for anti-cClqR/CaR on complement regulation. I gG derived from SLE serum reversed the inhibitory capacity of cClqR/Ca R in a dose-dependent fashion up to 63%, whereas IgG from normal donor s had no significant effect. With respect to the capacity of anti-cClq R/CaR antibodies to activate neutrophils, it was found that incubation of normal neutrophils with F(ab')(2) anti-cClqR/CaR resulted in a ver y limited oxidative burst. However, cross-linking of F(ab')(2) anti-cC lqR/CaR on the neutrophils clearly induced neutrophil activation. Pre- incubation of the SLE-derived F(ab')(2) with cClqR/CaR prevented activ ation of neutrophils up to 81 +/- 5%. These results suggest that the p resence of anti-cClqR/CaR antibodies in patients with SLE may modulate complement and neutrophil activation.