Background/Purpose:

Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (CCP) are important serum markers used in clinical diagnosis of rheumatoid arthritis (RA). Multiple studies have investigated previous generations of CCP assays, and several have shown CCP to be a highly specific and predictive marker for the diagnosis of RA. There are differences in sensitivity, specificity, and predictive value between the various generations of the CCP test. Previous studies of the CCP3.1 assay indicate that it may have a similar degree of specificity with a greater sensitivity than prior generations. However, these studies examined CCP levels in patients with already established RA. Our aim was to investigate the predictive value of the new CCP3.1 assay in identifying RA versus other conditions.

Methods:

We performed a retrospective systematic chart review of patients with a positive CCP level (≥20) from July 2016 to June 2017 at Cedars-Sinai Medical Center (CSMC) ordered by physicians from all specialties for any indication. Among those with a positive CCP, we investigated the different associated underlying diagnoses present at least 6 months after testing was performed, including RA and other autoimmune and non-autoimmune diagnoses. RA diagnoses were confirmed by a rheumatologist according to the 1987/2010 ACR criteria. The data was further stratified into low (≥20 and <40) and high (≥40) CCP levels and analyzed. Anti-CCP3.1 antibody levels were assessed using QUANTA Lite CCP 3.1 IgA/IgG ELISA (Inova Diagnostics, Inc., San Diego, CA). The tests were performed by ETI-Max 3000 analyzer with manual dilution of the specimens.

Results:

Of the 2027 CCP tests performed at CSMC, 307 positive CCP tests were reported among 281 unique patients. Among 281 patients, 48% (135/281) had a final diagnosis of RA, 46.3% (130/281) had a non-RA diagnosis, and 5.7% (16/281) did not have any diagnosis. 105 patients (37.4%) had a low CCP level, and 176 (62.6%) had a high CCP level. The positive predictive value of RA in patients with a high CCP (109/176, 61.9%) was 2.5-fold higher than those with a low CCP (26/105, 24.7%). Among the 130 non-RA diagnoses, the other most common autoimmune diseases included systemic lupus erythematosus (15.4%), primary Sjogren’s syndrome (8.5%) and polymyalgia rheumatica (3.8%). The most common non-autoimmune diagnoses were osteoarthritis (13.8%), interstitial lung disease (7.7%), malignancy (7.7%) and fibromyalgia (3.8%).

Conclusion:

Of the 281 patients with a positive CCP, nearly half were found to have a diagnosis other than RA. There seems to be a higher likelihood of RA with higher CCP levels. Overall, there were similar rates of autoimmune and non-immune mediated diseases between low and high CCP levels. Interestingly, certain autoimmune conditions, such as lupus, Sjogren’s and psoriatic arthritis were more likely to have a low CCP titer than a high one. Further research needs to be conducted to investigate the utility of this CCP3.1 assay.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/newer-generation-cyclic-citrullinated-peptide-ccp-3-1-assay-in-the-diagnosis-of-rheumatoid-arthritis/