Samuel Asamoah Sakyi, Tonnies Abeku Buckman, Daniel Antwi-Berko, Kwame Yeboah-Mensah, Dzifa Dey, Eddie-Williams Owiredu, Benjamin Amoani, Richard Mantey
{"title":"循环CD4+ T细胞中IL-6和IL-17A的胞浆内表达与类风湿关节炎的疾病活动密切相关并预测疾病活动:加纳的一项病例对照研究","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>IFN-<i>γ</i>, TNF-<i>α</i>, 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), <i>p</i> < 0.0001), IL-17A (0.00 (0.00-0.02) vs. 0.19 (0.09-0.30) vs. 0.99 (0.64-1.25), <i>p</i> < 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), <i>p</i> < 0.0001) increased significantly from the healthy controls through RA patients with low DAS scores to RA patients with moderate DAS scores. IL-6 (<i>β</i> = 0.681, <i>r</i> <sup>2</sup> = 0.527, <i>p</i> < 0.0001), IL-17A (<i>β</i> = 0.770, <i>r</i> <sup>2</sup> = 0.593, <i>p</i> < 0.0001), and IL-17A/IL-10 (<i>β</i> = 0.677, <i>r</i> <sup>2</sup> = 0.452, <i>p</i> < 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2020-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/2808413","citationCount":"6","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>IFN-<i>γ</i>, TNF-<i>α</i>, 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), <i>p</i> < 0.0001), IL-17A (0.00 (0.00-0.02) vs. 0.19 (0.09-0.30) vs. 0.99 (0.64-1.25), <i>p</i> < 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), <i>p</i> < 0.0001) increased significantly from the healthy controls through RA patients with low DAS scores to RA patients with moderate DAS scores. IL-6 (<i>β</i> = 0.681, <i>r</i> <sup>2</sup> = 0.527, <i>p</i> < 0.0001), IL-17A (<i>β</i> = 0.770, <i>r</i> <sup>2</sup> = 0.593, <i>p</i> < 0.0001), and IL-17A/IL-10 (<i>β</i> = 0.677, <i>r</i> <sup>2</sup> = 0.452, <i>p</i> < 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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":51715,\"journal\":{\"name\":\"International Journal of Rheumatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2020-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1155/2020/2808413\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Rheumatology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1155/2020/2808413\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Rheumatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2020/2808413","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 6
摘要
背景:T细胞因子在类风湿关节炎(RA)的发生发展中起重要作用。Th1/Th2和Th17/Treg平衡的丧失已在几种炎症性自身免疫性疾病中报道。然而，在迄今罕见的加纳背景下，它们在RA中的作用尚未得到探讨。在这里，我们评估了加纳类风湿性关节炎患者的胞浆内CD4+ T细胞细胞因子模式，并确定了它们与疾病活动性的关系。方法:本病例对照研究包括48名新诊断的RA患者和30名表面健康对照者，来自加纳两家主要医院。使用经过验证的结构化问卷来获取人口统计数据;采集血样进行流式细胞术分析。结果:RA患者中IFN-γ、TNF-α、IL-4、IL-6、IL-10、IL-17A、IL-6/IL-4、IL-17/IL-10的表达均显著高于健康对照组。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)、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)的表达水平从健康对照组到DAS评分较低的RA患者到DAS评分中等的RA患者均显著升高。IL-6 (β = 0.681, r 2 = 0.527, p < 0.0001)、IL-17A (β = 0.770, r 2 = 0.593, p < 0.0001)、IL-17A/IL-10 (β = 0.677, r 2 = 0.452, p < 0.0001)的表达与DAS28评分直接相关。IL-6(截止值= 1.32，灵敏度= 100.0%，特异度= 100.0%，准确度= 100.0%，AUC = 1.000)和IL-17A(截止值= 0.58，灵敏度= 100.0%，特异度= 100.0%，准确度= 100.0%，AUC = 1.000)在预测DAS中低评分方面具有最佳的区分能力。结论:Th1-和th17相关的细胞因子在RA的病理生理中起主导作用，IL-6和IL-17根据病情的严重程度主要表达，并有差异表达。在非洲地区，IL-6和IL-17A可作为有用的RA预后和疾病监测标志物。
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.
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, 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) 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.
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