REVIEW - Anti-CCP2 antibodies: an overview and perspective of the diagnostic abilities of this serological marker for early RA

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Clin Rev Allergy Immunol. 2008 February; 34(1): 36–39.

Published online 2007 September 18. doi: 10.1007/s12016-007-8029-y.

PMCID: PMC2243253

Anti-CCP2 Antibodies: An Overview and Perspective of the Diagnostic

Abilities of this Serological Marker for Early Rheumatoid Arthritis

Walther J. van Venrooij and Albert J.W. Zendman

Department of Biomolecular Chemistry, Radboud University Nijmegen,

Nijmegen, The Netherlands

..

Abstract

The literature of the last 4 years confirms that the anti-CCP2 test is

a very useful marker for the early and specific diagnosis of

rheumatoid arthritis (RA). The anti-CCP2 test is very specific for RA

(95–99%) and has sensitivity comparable to that of the rheumatoid

factor (70–75%). The antibodies can be detected very early in the

disease and can be used as an indicator for the progression and

prognosis of RA. In this review, these interesting properties and some

future possibilities of this diagnostic test are discussed.

The presence of autoantibodies in the serum of patients is a very

typical phenomenon for autoimmune diseases. Most of these

autoantibodies, however, can also be detected in patients with other

conditions and are therefore not specific. A typical example is the

rheumatoid factor (RF), which is present in most inflammatory

conditions. However, in some cases, autoantibodies can give the

clinician a more precise indication of the type of underlying disease

because they occur specifically in a certain disease. For example,

anti-Sm antibodies are linked almost exclusively to systemic lupus

erythematosus (SLE); whereas anti-DNA topoisomerase-I antibodies are

typically present in scleroderma patients. Among the most

disease-specific autoantibodies described are the so-called ACPA

(anti-citrullinated protein/peptide antibodies). These antibodies

occur specifically in RA and can be measured most conveniently via the

anti-CCP (anti-cyclic citrullinated peptide) antibody test.

The first generation CCP test (CCP1) used in early diagnostic studies

(2000–2001) contained a single cyclic citrullinated peptide derived

from filaggrin as the substrate [1]. It could detect ACPA in 68% of

patients with established RA with a very high specificity (98%).

Because filaggrin is not expressed in the synovium, it is most likely

not the natural citrullinated antigen for ACPA. Other peptides, not

related to filaggrin, could therefore potentially provide better

epitopes for detection of ACPA. Via screening of a number of peptide

libraries, novel citrullinated peptides were obtained and incorporated

into a second generation CCP test (CCP2). This test is commercially

available, and as all companies use the same type of CCP2 peptides,

standardization is achieved quite easily. The diagnostic properties of

this test will be discussed below.

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