English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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.

Autoantibodies against C1q in Systemic Lupus Erythematosus Are Antigen-Driven