Rheumatoid Arthritis Serology in Macedonian Patients with Rheumatoid Arthritis: Rheumatoid Factor, Anti-Cyclic Citrulinated Peptide Antibodies or both?

Abstract

Introduction: In the last 70 years, Rheumatoid Factor (RF) was considered the most useful laboratory marker in patients with rheumatoid arthritis (RA). The next very important milestone for the RA diagnosis was the discovery of anti-citrullinated peptide/protein antibodies (ACPA). The detection of ACPA is usually done with the CCP test of the second generation, CCP2.

Objective: To evaluate the performances of RF and CCP2 tests and to see whether or not the performance of both tests together is better then the performances of either of the tests alone.

Materials and Methods: We performed a cross-sectional study with 380 participants of which 155 RA patients who fulfilled the American College of Rheumatology (ACR) 1987 classification criteria for RA, 120 patients with inflammatory and other connective tissue diseases (Non-RA) and 105 healthy controls (HC), at the Rheumatology Clinic in Skopje, Macedonia. The patients and controls were tested for RF and ACPA.

Results: The mean age of the RA patients was 50 years, and 87 % of the patients were female. The average duration of the disease has been 6 years. In this group of patients, CCP2 test showed identical sensitivity of 0,69 and better specificity than RF (0,95 vs. 0,87 respectively). For the patients who tested positive for both tests, the sensitivity was lower 0,60 and for the patients who were either ACPA or RF positive, sensitivity was slightly higher 0,73. The specificity of 0,88 for both or either of the tests was identical with that of RF. The positive likelihood ratio was 13,8 for the CCP2 test, 5,3 for RF and 5,1 for both tests done together. Ninety four out of 155 RA patients were positive for both ACPA and RF, 20 patients were positive for either one of the antibodies of which 7 (4,5%) RA patients were only anti-CCP positive and 13 (8,3%) patients were only RF positive.

Conclusion: The results from our study showed that the sensitivity and specificity of both tests, done in parallel, does not differ much from the sensitivity of either of the tests alone and from the specificity of RF, respectfully. Still, CCP2 test showed the highest specificity and positive likelihood ratio as was expected. The results from our study support the idea that in countries like Macedonia, which can not afford enough CCP2 antibody kits, we may use RF first, especially in patients who are not likely to meet any clinical criteria for RA. In patients with early undifferentiated arthritis or early RA we may use both antibodies in order to select the patients who will need more aggressive treatment.