title: Anti-C1q autoantibodies from systemic lupus erythematosus patients activate the complement system via both the classical and lectin pathways.
abstract: Autoantibodies against complement C1q (anti-C1q) strongly correlate with the occurrence of lupus nephritis and hypocomplementemia in systemic lupus erythematosus (SLE). Although a direct pathogenic role of anti-C1q has been suggested, the assumed complement-activating capacity remains to be elucidated. Using an ELISA-based assay, we found that anti-C1q activate the classical (CP) and lectin pathways (LP) depending on the anti-C1q immunoglobulin-class repertoire present in the patient's serum. IgG anti-C1q resulted in the activation of the CP as reflected by C4b deposition in the presence of purified C1 and C4 in a dose-dependent manner. The extent of C4b deposition correlated with anti-C1q levels in SLE patients but not in healthy controls. Our data indicate that SLE patient-derived anti-C1q can activate the CP and the LP but not the alternative pathway of complement. These findings are of importance for the understanding of the role of anti-C1q in SLE suggesting a direct link to hypocomplementemia.
authors.affiliation: Laboratory of Clinical Immunology, University Hospital Basel, CH-4031 Basel, Switzerland. Electronic address: sophia.thanei@unibas.ch.
authors.forename: Sophia
authors.initials: S
authors.lastname: Thanei
authors.affiliation: Laboratory of Clinical Immunology, University Hospital Basel, CH-4031 Basel, Switzerland; Ludwig Center for Cancer Research, University of Lausanne, CH-1066 Lausanne, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Vanhecke
authors.affiliation: Laboratory of Clinical Immunology, University Hospital Basel, CH-4031 Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, CH-4031 Basel, Switzerland.
authors.forename: Marten
authors.initials: M
authors.lastname: Trendelenburg
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000276:immunology*; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015922:Complement C1q
keywords: Anti-C1q; Classical pathway; Complement; Lectin pathway; Lupus nephritis; Systemic lupus erythematosus