RESEARCH - Anti-CCP antibodies from RA patients activate complement via both the classical and alternative pathways

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Arthritis Rheum. 2009 Jun 29;60(7):1923-1931.

Anti-cyclic citrullinated peptide antibodies from rheumatoid arthritis

patients activate complement via both the classical and alternative

pathways.

Trouw LA, Haisma EM, Levarht EW, van der Woude D, Ioan-Facsinay A,

Daha MR, Huizinga TW, Toes RE.

Leiden University Medical Center, Leiden, The Netherlands.

OBJECTIVE: It has been suggested that anti-citrullinated protein

antibodies (ACPAs) play an important role in the pathogenesis of

rheumatoid arthritis (RA). To exert their pathologic effects, ACPAs

must recruit immune effector mechanisms such as activation of the

complement system. Mouse models of RA 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-CCP) 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-CCP antibodies, using cyclic citrullinated peptide-coated plates,

specific buffers, and normal and complement-deficient sera as a source

of complement.

RESULTS: Anti-CCP 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-CCP antibodies. Complement activation proceeded in

vitro up to the formation of the membrane attack complex, indicating

that all activation steps, including the release of C5a, took place.

CONCLUSION: Our findings indicate that anti-CCP 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 RA.

PMID: 19565507

http://www.ncbi.nlm.nih.gov/pubmed/19565507

Not an MD

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nice info, however even me who is in the medical field does not get it

LOL

Kathy