Background/Purpose:

The diagnosis of anti-CCP antibody (ACPA) negative rheumatoid arthritis (RA) are known to be difficult and delayed as compared with ACPA-positive RA. This study was designed to evaluate serum levels of cytokines/chemokines and to establish a new discriminating system of ACPA-negative RA patients from non-RA arthritic patients and healthy controls.

Methods:

A total of 174 RA patients (mean DAS28-CRP = 2.67; 104 ACPA-positive and 70 ACPA-negative patients) diagnosed according to the ACR/EULAR 2010 classification criteria for RA, 33 non-RA arthritic (NRA) patients including seronegative spondyloarthropathy (SNSA), and 76 sex-matched healthy controls (HC) were included. By using a chemi-luminescence immunoassay, twenty-eight cytokines/chemokines, including IFN-g, TNF-a, IL-1b, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-17F, IL-23, CCL20, CXCL13, TGF-b1, were measured in the sera of the above populations. Results were analyzed by Mann-Whitney U-test. Discriminant analysis was performed using multiple logistic regression analysis.

Results:

Our study revealed that (1) several cytokines/ chemokines, including IFN-g, TNF-a and novel cytokines were upregulated in RA patients as compared with in healthy controls. (2) Multiple logistic regression analysis revealed that the combinations of three to five cytokines/chemokines could clearly discriminate not only ACPA-positive but also ACPA-negative RA patients from NRA patients as well as RA patients from HC (Figure 1);ACPA-negative RA: 70, NRA: 33, HC:76).

Conclusion:

Our study using a chemi-luminescence immunoassay led to the identification of cytokine/chemokine profiles useful in the differential diagnosis of ACPA-negative RA from non-RA arthritis.