Anti-cyclic citrullinated peptide antibodies from XXXX patients activate complement via both the classical and alternative pathways.

@entity19 @entity2242 @entity465 @entity5810 @entity309
OBJECTIVE: It has been suggested that anti-citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of @entity309 ( @entity309 ). To exert their pathologic effects, ACPAs must recruit immune effector mechanisms such as activation of the complement system. @entity19 models of @entity309 have shown that, surprisingly, arthritogenic antibodies activate the alternative pathway of complement rather than the expected classical pathway. This study was undertaken to investigate whether human anti-cyclic citrullinated peptide (anti- @entity5810 ) antibodies activate the complement system in vitro and, if so, which pathways of complement activation are used. METHODS: We set up novel assays to analyze complement activation by anti- @entity5810 antibodies, using cyclic citrullinated peptide-coated plates, specific buffers, and normal and @entity465 sera as a source of complement. RESULTS: Anti- @entity5810 antibodies activated complement in a dose-dependent manner via the classical pathway of complement, and, surprisingly, via the alternative pathway of complement. The lectin pathway was not activated by anti- @entity5810 antibodies. Complement activation proceeded in vitro up to the formation of the membrane attack complex, indicating that all activation steps, including the release of @entity2242 , took place. CONCLUSION: Our findings indicate that anti- @entity5810 antibodies activate the complement system in vitro via the classical and alternative pathways but not via the lectin pathway. These findings are relevant for the design of interventions aimed at inhibition of complement-mediated damage in @entity309 .
