Abstract
ObjectiveAnti-cyclic citrullinated peptide 2 antibodies (anti-CCP2) and rheumatoid factor (RF) in rheumatoid arthritis (RA) has been extensively assessed in industrialized countries. We investigated the diagnostic and prognostic impact of anti-CCP2 and RF isotypes in a Sudanese cross-sectional RA cohort.MethodsConsecutive RA patients (n = 281) diagnosed according to the 1987 ACR criteria were included 2008–2010. Anti-CCP2 and RF isotypes (IgA, IgM, and IgG) were measured by enzyme immunoassay in 262 patients, with reference intervals aligned to the same diagnostic specificity as for anti-CCP2 (97.6%) using national controls.ResultsIgA RF was the predominant RA-associated autoantibody (56%), followed by IgM RF and anti-CCP2 (both 52%) and IgG RF (49%). In receiver operator characteristic analysis, IgA RF also showed the largest area under the curve. Patients with IgG RF were younger and had 8 years lower median age of disease onset compared to antibody negative patients (p < 0.0001). IgG RF was the only marker associated with a high number of involved joints (p = 0.028), and together with anti-CCP2 were the strongest markers for finger deformities (p = 0.016 and p = 0.012), respectively. No statistical differences were found for disease duration, ESR and Hb levels, and occurrence of erosions/osteopenia for any of the investigated autoantibodies.ConclusionWhereas IgA RF showed the best diagnostic performance, IgG RF associated with low age of RA onset, high number of involved joints, and finger deformities. These findings indicate that RA-associated antibodies other than conventional IgM RF and anti-CCP2 might be informative in non-Caucasian RA populations.
Highlights
The autoantibody rheumatoid factor (RF) was the first described rheumatoid arthritis (RA)-associated marker and included in the 1987 classification criteria of the American College of Rheumatology (ACR) [1]
The diagnostic utility of the most commonly used anti-cyclic citrullinated protein/peptide antibodies (ACPA) test measuring antibodies against cyclic citrullinated peptide 2 and RF were investigated in systemic reviews performed by Avouac et al and Nishimura et al These studies concluded that anti-CCP2 was a better marker for RA diagnosis [5, 6] as well as a better predictor of bone erosions [6] than RF in cohorts mainly encompassing Caucasian RA patients
We found that IgA RF was the diagnostically most sensitive autoantibody followed by anti-CCP2 and IgM RF and by IgG RF (49.8%), after that reference intervals had been adjusted to the same diagnostic specificity
Summary
The autoantibody rheumatoid factor (RF) was the first described rheumatoid arthritis (RA)-associated marker and included in the 1987 classification criteria of the American College of Rheumatology (ACR) [1]. The diagnostic utility of the most commonly used ACPA test measuring antibodies against cyclic citrullinated peptide 2 (anti-CCP2) and RF were investigated in systemic reviews performed by Avouac et al and Nishimura et al These studies concluded that anti-CCP2 was a better marker for RA diagnosis [5, 6] as well as a better predictor of bone erosions [6] than RF in cohorts mainly encompassing Caucasian RA patients. Low levels of autoantibodies are found in healthy control populations, and to perform proper comparison of performance, the different measures should be aligned to show the same diagnostic specificity in relation to control groups It is a common perception among clinical pathologists that levels of clinical laboratory measures differ between populations [7,8,9], and autoantibody reference intervals should preferably be set in relation to geographically matched control groups
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