Improving RA Diagnosis With Use of Anti-ACPAs

In patients with rheumatoid arthritis, the use of multiple antibody assays may improve clinical diagnosis and disease management.

In patients with rheumatoid arthritis (RA), the use of multiple antibody assays may improve clinical diagnosis and disease management, according to a study published in Arthritis & Rheumatology.

Detection of antibodies to citrullinated protein/peptide antigens (ACPAs) is one of the diagnostic criteria for RA. These antibodies can be measured with the use of such generic tests as cyclic citrullinated peptide (CCP) assays. These tests, which provide good specificity and sensitivity, use artificially generated synthetic peptides with no homology to known proteins. In contrast, peptides from real auto-antigens, known as “fine specificities,” tend to be of lower diagnostic sensitivity and are used mainly for research into the pathogenesis of RA, rather than for the clinical management of patients with the disease.

In a previous study by the same group, 2 groups of ACPA fine specificities were found to be associated with different risk factors for RA. The investigators sought to explore whether testing for these 2 fine specificities (citrullinated enolase peptide-1 [CEP-1] and citrullinated peptide from tenascin-C [cTNC5]) in combination with anti-CCP would improve the diagnosis of patients with RA or help identify clinical subsets of patients with the disorder.

Prior data from a total of 287 patients with RA and 330 control individuals with osteoarthritis were analyzed for levels of anti-CEP-1, and the sera collected from the patients were retested with use of a commercially available anti-CEP-1 enzyme-linked immunosorbent assay. Diagnostic sensitivity for anti-CEP-1 was increased from 39% to 48% with the use of the commercial assay; the specificity was 98%.

Examining whether addition of anti-CEP-1 and anti-cTNC5 to anti-CCP2 increased overall diagnostic sensitivity, researchers identified 8 patients with RA who were negative for anti-CCP2, but were positive for either or both of the fine specificities. This finding increased the overall diagnostic sensitivity for ACPA from 84% with the use of anti-CCP alone to 87% when all 3 assays were combined.

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The investigators also examined whether assaying patients with anti-CEP-1 and/or anti-cTNC5 could identify distinct subsets of patients with RA. In this analysis, those patients who were anti-CCP-negative were not included, as those numbers were too small for statistical assessment. No difference in joint disease was observed between those patients who were anti-cTNC5-positive compared with those who were anti-CEP-1-positive. The 28-joint disease activity score of individuals who were positive for all 3 markers increased when both fine specificities were combined with anti-CCP2 levels vs those individuals who were positive for CCP2 only (P =.038). Patients who were positive for anti-CCP2, anti-CEP1, and cTNC5 had higher levels of anti-CCP2 and anti-rheumatoid factors antibodies (P <.001 for both).

“We suggest that the only way to establish whether fine specificities are useful in improving diagnosis or identifying clinical subsets, is to adopt at least these two fine specificities into prospective studies, so that in RA, multiple antibody assays become routine parts of clinical diagnosis and management,” noted the study investigators.

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Schwenzer A, Quirke AM, Montgomery AB, et al. Time to include fine specificity ACPAs in the routine diagnosis and management of rheumatoid arthritis? [published online October 31, 2018]. Arthritis Rheumatol. doi: 10.1002/art.40767