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

Samuel Asamoah Sakyi; Tonnies Abeku Buckman; Daniel Antwi-Berko; Kwame Yeboah-Mensah; Dzifa Dey; Eddie-Williams Owiredu; Benjamin Amoani; Richard Mantey

doi:10.1155/2020/2808413

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

Int J Rheumatol. 2020 Oct 8:2020:2808413. doi: 10.1155/2020/2808413. eCollection 2020.

Authors

Samuel Asamoah Sakyi¹, Tonnies Abeku Buckman¹, Daniel Antwi-Berko², Kwame Yeboah-Mensah³, Dzifa Dey⁴, Eddie-Williams Owiredu¹, Benjamin Amoani⁵, Richard Mantey¹

Affiliations

¹ Department of Molecular Medicine, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
² Department of Basic and Applied Biology, University of Energy and Natural Resources, Sunyani, Ghana.
³ Department of Medicine, School of Medicine and Dentistry, Komfo Anokye Teaching Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
⁴ Department of Medicine and Therapeutics, Korle-Bu Teaching Hospital, University of Ghana Medical School, Accra, Ghana.
⁵ Department of Biomedical Sciences, College of Health and Allied Sciences, School of Allied Health Sciences, University of Cape Coast, Cape Coast, 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 hitherto rare 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 apparent 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 expressions 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, r ² = 0.527, p < 0.0001), IL-17A (β = 0.770, r ² = 0.593, p < 0.0001), and IL-17A/IL-10 (β = 0.677, r ² = 0.452, p < 0.0001) expressions were significantly directly associated with DAS28 scores. IL-6 (cutoff = 1.32, sensitivity = 100.0%, specificity = 100.0%, accuracy = 100.0%, and AUC = 1.000) and IL-17A (cutoff = 0.58, sensitivity = 100.0%, specificity = 100.0%, accuracy = 100.0%, and 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.