Intracytoplasmic expression of IL-6 and IL-17A in circulating CD4+ T cells are strongly associated with and predict disease activity in rheumatoid arthritis: A case-control study in Ghana

Abstract

Background T cell cytokines play important roles in the development and progression of rheumatoid arthritis (RA). Loss of Th1/Th2 and Th17/Treg balance has been reported in several in ammatory autoimmune diseases. However, their role in RA within the Ghanaian context has not been explored. Here, we evaluated the intracytoplasmic CD4 + T cell cytokine patterns in rheumatoid arthritis patients in Ghana and determined their relationship with disease activity. Methods This case-control study included 48 newly-diagnosed RA patients and 30 healthy controls from two major hospitals in Ghana. Validated structured questionnaires were administered to obtain demographic data; blood samples were collected and processed for ow cytometric analysis. Results IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17A, IL-6/IL-4 and IL-17/IL-10 expression were signi cantly higher in RA cases compared to the healthy controls. The expression of IL-6 (0.00 (0.00-0.98) vs 0.82 (0.34–1.10) vs 1.56 (1.39–1.68), p < 0.0001), IL-17A (0.00 (0.00-0.02) vs 0.19 (0.09–0.30) vs 0.99 (0.64–1.25), p < 0.0001) and IL-17A/IL-10 (0.00 (0.00-0.39) vs 0.15 (0.09–0.26) vs 0.88 (0.41–1.47), p < 0.0001) increased signi cantly from the healthy controls through RA patients with low DAS scores to RA patients with moderate DAS scores. IL-6 (β = 0.681, r2 = 0.527, p < 0.0001), IL-17A (β = 0.770, r2 = 0.593, p < 0.0001) and IL-17A/IL-10 (β = 0.677, r2 = 0.452, p < 0.0001) expression were signi cantly directly associated with DAS28 scores. IL-6 (Cutoff = 1.32, Sensitivity = 100.0%, Speci city = 100.0%, Accuracy = 100.0%, AUC = 1.000) and IL-17A (Cutoff = 0.58, Sensitivity = 100.0%, Speci city = 100.0%, Accuracy = 100.0%, AUC = 1.000) presented with the best discriminatory power in predicting moderate DAS scores from low DAS scores. Conclusion Th1 and Th17 related cytokines predominate in the pathophysiology of RA; with IL-6 and IL-17 being principally and differentially expressed based on the severity of the disease. IL-6 and IL-17A could serve as useful prognostic and disease-monitoring markers in RA in the African context.