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ARTICLE
Distinct serum chemokine signatures differentiate rheumatoid arthritis from non-rheumatoid arthritides
Hitoshi Uga1,*, Takahiro Okazawa1, Yoshiaki Miyamoto1, Takehiro Hasegawa1, Jun Saegusa2, Akio Morinobu2,3, Shunichi Kumagai4, Hirokazu Kurata1,5
1 Central Research Laboratories, Sysmex Corporation, Kobe, Japan
2 Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan
3 Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
4 The Center for Rheumatic Diseases, Shinko Hospital, Kobe, Japan
5 Department of Internal Medicine, Higashi-Kobe Hospital, Kobe, Japan
* Corresponding Author: Hitoshi Uga. Email: 
European Cytokine Network https://doi.org/10.32604/ecn.2026.083162
Received 30 March 2026; Accepted 05 June 2026; Published online 09 July 2026
Abstract
Background: Early and accurate differential diagnosis of rheumatoid arthritis (RA) remains challenging, particularly in patients with seronegative or non-specific inflammatory arthritides. Because cytokines and chemokines play central roles in immune activation and leukocyte trafficking, we investigated whether serum cytokine and chemokine profiles could discriminate RA from non-rheumatoid arthritides (NRA) and healthy controls (HCs). Methods: One hundred and fifty-seven RA patients (104 anti-cyclic citrullinated peptide antibody (ACPA)-positive and 53 ACPA-negative patients), 33 NRA patients and 86 HCs were included. Fourteen cytokines and twelve chemokines were measured in the sera of the above three cohorts, using high-sensitivity chemi-luminescence immunoassay. Results were analyzed by non-parametric Mann-Whitney U-test and multiple logistic regression analysis. Results: Among the parameters, eight chemokines (CCL3, 4, 11, 20, 27, CXCL9, 10 and 13) were significantly upregulated in RA patients as compared with NRA patients and HCs (Mann-Whitney U-test: p < 0.01). Multiple logistic regression analysis revealed that the combination of four chemokines (CCL3, 11, 27 and CXCL13) can effectively discriminate RA from NRA patients and HCs (Area Under the Curve (AUC) = 0.92), as well as ACPA-negative RA from NRA patients (AUC = 0.73). Conclusions: A serum four-chemokine signature consisting of CCL3, CCL11, CCL27, and CXCL13 discriminated RA, including ACPA-negative RA, from non-rheumatoid arthritides and healthy controls. These findings suggest that serum chemokine profiling may provide adjunctive diagnostic information for the differential diagnosis of RA.
Keywords
Chemokine; rheumatoid arthritis; differential diagnosis; logistic regression analysis
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