title: Anti-C1q receptor/calreticulin autoantibodies in patients with systemic lupus erythematosus (SLE).
abstract: 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 Clq, 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.
authors.affiliation: Department of Nephrology, Leiden University Hospital, The Netherlands.
authors.forename: R H
authors.initials: RH
authors.lastname: van den Berg
authors.forename: C E
authors.initials: CE
authors.lastname: Siegert
authors.forename: M C
authors.initials: MC
authors.lastname: Faber-Krol
authors.forename: T W
authors.initials: TW
authors.lastname: Huizinga
authors.forename: L A
authors.initials: LA
authors.lastname: van Es
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
mesh_terms: D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000276:immunology*; D037282:Calreticulin; D002352:Carrier Proteins; D003167:Complement Activation / Q000276:immunology; D015922:Complement C1q / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006461:Hemolysis; D006801:Humans; D018960:Hyaluronan Receptors; D007128:Immunoglobulin Fragments / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology*; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; C087299:C1QBP protein, human; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D007128:Immunoglobulin Fragments; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D012261:Ribonucleoproteins; C032402:complement 1q receptor; D015922:Complement C1q