EDITORIAL - Anti-CCP in preclinical RA: food for thought

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Journal of Rheumatology

doi: 10.3899/jrheum.090184

01 Apr 2009 vol. 36 no. 4 663-664

Anti-Cyclic Citrullinated Peptide in Preclinical Rheumatoid Arthritis.

Food for Thought

Citrullinated (cit-) epitope detection is an evolving science with

different substrates being proposed continuously1–4. Given all the

published enthusiasm with anti-cyclic citrullinated peptide (CCP), why

does the test need to be improved? It is assumed that the cit-epitopes

targeted in cit-peptides/proteins are all detected by anti-CCP and are

invariable in the various individuals during the phases of disease.

That premise may be incorrect.

Recent objective critical evaluation of anti-CCP is severe. Its added

value in rheumatoid arthritis (RA) diagnostics, over and above

previously existing clinical and laboratory tools, is deemed

marginal5. The huge anti-CCP literature contains recurring

inconsistencies suggesting that authors are using the same test to

measure different things in a very heterogeneous disease. Moreover, it

is difficult to understand how a test can be associated with more

severe evolution in early RA6 and also be positive without arthritis

for 10 to 15 years before people get sick7–10. How does one reconcile

that?

The solution of Chibnik, et al in this issue of The Journal7 is to pay

more attention to titers of anti-CCP to explain the transition from

pre-RA to RA. Just having anti-CCP is not sufficient; also important

is how much one has. The higher the titer, the shorter the interval to

disease onset! Titers rise steadily until disease onset and then

stabilize, as is the current experience in established disease. That

the titers rise near RA onset has already been suggested8 and is

convincingly confirmed here7. What does that mean exactly? Either the

disease manifests itself only when a sufficient level of autoantibody

is reached (quantitative change) or when a given autoantibody emerges

whose specificity is associated with disease onset (qualitative

change). The 2 explanations are not mutually exclusive, as maturation

of an immune response is accompanied by rising titers and epitope

dominance.

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Read the full article here:

http://www.jrheum.org/content/36/4/663.long

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