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 inflammatory 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 flow 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 significantly 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 significantly 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 significantly directly associated with DAS28 scores. IL-6 (Cutoff = 1.32, Sensitivity = 100.0%, Specificity = 100.0%, Accuracy = 100.0%, AUC = 1.000) and IL-17A (Cutoff = 0.58, Sensitivity = 100.0%, Specificity = 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.

A Natural Plant Ingredient, Menthone, Regulates T Cell Subtypes and Lowers Pro-inflammatory Cytokines of Rheumatoid Arthritis

“…However, Th1, Th2, Th17, and Treg cells, as four important subtypes of CD4 + T cells, are closely associated with the occurrence and development of RA. 37,38 Studies have found that Th1 and Th17 cells play an important role in the development of RA, while Th2 and Treg cells may play a protective role in RA patients. 39 Therefore, RA patients often have an imbalance in the number of Th1, Th2, Th17, and Treg cells.…”