Circulating CD4+ FoxP3– CXCR5– CXCR3+ PD‐1hi cells are elevated in active rheumatoid arthritis and reflect the severity of the disease

Abstract

Objective To examine the expression and clinical significance of circulating CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells in rheumatoid arthritis (RA). Methods CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells in peripheral blood of 35 patients with active RA, 17 with RA in stable remission, and 24 healthy controls were analyzed by flow cytometry. Serum IgG and circulating plasmablast percentages were measured and correlations with CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells were systematically analyzed. Disease Activity Scale 28 (DAS28) scores were also calculated and correlation analysis with CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells was conducted. The levels of CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells were compared before and after disease-modifying anti-rheumatic drug treatment. Cytokine levels in plasma and cytokine secretion in CD4 cells were measured and their correlations with CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells were further analyzed. Results The levels of CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells in the peripheral blood of patients with active RA were significantly increased compared with healthy controls. CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells in patients with active RA were positively correlated with serum IgG and DAS28 scores. CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells were significantly decreased in patients after treatment. Plasma interleukin-10 concentrations and interleukin-10-positive CD4 cell percentages were significantly positively correlated with CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cell levels. Conclusion Circulating CD4⁺ FoxP3^– CXCR5^– CXCR3⁺ PD-1^hi cells in patients with active RA are increased and could reflect the severity of the disease, which may play a potential role in the pathogenesis of RA.