Anti‐C1q receptor/calreticulin autoantibodies in patients with systemic lupus erythematosus (SLE)

• Published in: Clinical and experimental immunology 1998-02, Vol.111 (2), p.359-364
• Main Authors: VAN DEN BERG, R. H, SIEGERT, C. E. H, FABER-KROL, M. C, HUIZINGA, T. W. J, VAN ES, L. A, DAHA, M. R
• Format: Article
• Language: English
• Subjects: Antibody Specificity; autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Biological and medical sciences; C1q receptor; Calcium-Binding Proteins - immunology; Calreticulin; Carrier Proteins; complement; Complement Activation - immunology; Complement C1q - immunology; Enzyme-Linked Immunosorbent Assay; Hemolysis; human; Humans; Hyaluronan Receptors; Immunoglobulin Fragments - pharmacology; lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Medical sciences; Membrane Glycoproteins; Mitochondrial Proteins; Neutrophil Activation - immunology; neutrophils; Neutrophils - immunology; Original; Receptors, Complement - immunology; Ribonucleoproteins - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sensitivity and Specificity
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1998.00473.x

SLE is a disease characterized by the presence of multiple autoantibodies and high levels of circulating immune complexes. We studied the presence and functional relevance of autoantibodies directed against a receptor for the collagen‐like stalks of the first subcomponent of complement, also known as calreticulin (cC1qR/CaR), in patients with SLE. In a cross‐sectional study it was found that higher titres of antibodies against cC1qR/CaR are present in sera of SLE patients compared with normal donors. No association between anti‐cC1qR/CaR titres and SLE disease activity was found. Following gel filtration of SLE serum it was found that anti‐cC1qR/CaR reactivity is associated with the peak of monomeric IgG. Purified IgG from patients was able to specifically immunoprecipitate cC1qR/CaR. Since we have shown previously that cC1qR/CaR is able to inhibit the haemolytic activity of C1q, we determined a possible pathogenic role for anti‐cC1qR/CaR on complement regulation. IgG derived from SLE serum reversed the inhibitory capacity of cC1qR/CaR in a dose‐dependent fashion up to 63%, whereas IgG from normal donors had no significant effect. With respect to the capacity of anti‐cC1qR/CaR antibodies to activate neutrophils, it was found that incubation of normal neutrophils with F(ab′)2 anti‐cC1qR/CaR resulted in a very limited oxidative burst. However, cross‐linking of F(ab′)2 anti‐cC1qR/CaR on the neutrophils clearly induced neutrophil activation. Pre‐incubation of the SLE‐derived F(ab′)2 with cC1qR/CaR prevented activation of neutrophils up to 81 ± 5%. These results suggest that the presence of anti‐cC1qR/CaR antibodies in patients with SLE may modulate complement and neutrophil activation.