Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven

Schaller, Monica and Bigler, Cornelia and Danner, Doris and Ditzel, Henrik J. and Trendelenburg, Marten. (2009) Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven. Journal of immunology : official journal of the American Association of Immunologists, Vol. 183. pp. 8225-8231.

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Official URL: http://edoc.unibas.ch/dok/A6005656

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Autoantibodies against complement C1q (anti-C1q Abs) were shown to strongly correlate with the occurrence of severe nephritis in patients with systemic lupus erythematosus (SLE), suggesting a potential pathogenic role by interfering with the complement cascade. To analyze the humoral immune response against C1q at the molecular level, we screened a bone marrow-derived IgGkappa/IgGlambda Fab phage display library from a SLE patient with high anti-C1q Ab titer against purified human C1q. Six Fabs that exhibited strong binding to C1q in ELISA were isolated. The anti-C1q Fabs recognized neoepitopes that were only exposed on bound C1q and not present on soluble C1q mapping to different regions of the collagen-like region of C1q. Analysis of the genes encoding the variable H and L chains of the IgG-derived anti-C1q Fab revealed that all the variable H and L chain regions were highly mutated, with nucleotide and amino acid homologies to the closest germline in the range of 71-97% (average 85 +/- 4) and 72-92% (average 88 +/- 6), respectively. In addition, the variable region of the Fabs exhibited high replacement to silent ratios. The six anti-C1q Fabs were shown to be of high affinity, with a K(d) ranging from of 8.4 x 10(-8) M to 1.4 x 10(-7) M, comparable to an antiviral immune response. Our data underlines the notion that the development of anti-C1q Abs in SLE is the consequence of an Ag-driven, affinity-matured immune response. Those anti-C1q Fabs are unique tools to address how complement C1q is implicated in the pathogenesis of SLE.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Immunology (Trendelenburg)
UniBasel Contributors:Trendelenburg, Marten
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Assoc. of Immunologists
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:13

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