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Activated inducible co-stimulator-positive programmed cell death 1-positive follicular helper T cells indicate disease activity and severity in ulcerative colitis patients.
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-07-04 , DOI: 10.1111/cei.13485
Y Long 1 , X Zhao 1 , Chang Liu 1 , C Xia 1 , Chen Liu 1
Affiliation  

Inducible co‐stimulator‐positive (ICOS) and programmed cell death 1‐positive (PD‐1) are important markers for follicular helper T cells (Tfh); however, their roles and clinical values in ulcerative colitis (UC) remain unknown. In this study, we recruited 68 UC patients and 34 healthy controls. Circulating ICOS+, PD‐1+ and ICOS+PD‐1+ Tfh subsets were analyzed by flow cytometry. Twelve active UC patients achieving remission after treatment with 5‐aminosalicylic acid were followed‐up and Tfh subset changes were analyzed. Serum immunoglobulin (Ig)G, C‐reactive protein (CRP), interleukin (IL)‐4 and IL‐21 levels and B cell subsets were analyzed and Mayo scores were calculated. Correlation analyses were performed between Tfh subsets and the clinical indicators. Receiver operating characteristic (ROC) curves were generated to evaluate the efficiency of Tfh subsets for disease monitoring. We found that levels of ICOS+, PD‐1+ and ICOS+PD‐1+ Tfh cells were significantly increased in active UC and significantly decreased when achieving clinical remission. Activated ICOS+PD‐1+Tfh cells were positively correlated with serum CRP and Mayo scores. Furthermore, ICOS+PD‐1+ Tfh cells were significantly correlated with circulating new memory B cells and plasmablasts, as well as serum IgG, IL‐4 and IL‐21. ROC analyses showed that when ICOS+PD‐1+ Tfh cells were used in combination with PD‐1+ Tfh cells, the diagnostic efficacy in distinguishing active UC from stable remission patients was higher than that of any one used alone, with area under curve (AUC) value 0·931. Our findings suggest that increased ICOS+PD‐1+ Tfh cells are associated with the activation of B cells in the pathogenesis of UC, and may be a potential biomarker for UC disease monitoring.

中文翻译:

激活的诱导型共刺激阳性程序性细胞死亡 1 阳性滤泡辅助 T 细胞表明溃疡性结肠炎患者的疾病活动性和严重程度。

可诱导共刺激阳性 (ICOS) 和程序性细胞死亡 1 阳性 (PD-1) 是滤泡辅助 T 细胞 (Tfh) 的重要标志物;然而,它们在溃疡性结肠炎(UC)中的作用和临床价值仍然未知。在这项研究中,我们招募了 68 名 UC 患者和 34 名健康对照者。流通ICOS +、PD-1 +和ICOS + PD-1 +通过流式细胞术分析 Tfh 亚群。对 12 名在用 5-氨基水杨酸治疗后达到缓解的活动性 UC 患者进行随访,并分析了 Tfh 亚群的变化。分析血清免疫球蛋白 (Ig)G、C 反应蛋白 (CRP)、白细胞介素 (IL)-4 和 IL-21 水平以及 B 细胞亚群,并计算 Mayo 评分。在 Tfh 子集和临床指标之间进行相关分析。生成接收器操作特征 (ROC) 曲线以评估 Tfh 子集用于疾病监测的效率。我们发现ICOS +、PD-1 +和ICOS + PD-1 + Tfh 细胞水平在活动期UC 中显着增加,在达到临床缓解时显着降低。激活ICOS+ PD-1 + Tfh 细胞与血清 CRP 和 Mayo 评分呈正相关。此外,ICOS + PD-1 + Tfh 细胞与循环的新记忆 B 细胞和浆母细胞以及血清 IgG、IL-4 和 IL-21 显着相关。ROC分析表明,当ICOS + PD-1 + Tfh细胞与PD-1 + Tfh细胞联合使用时,区分活动性UC和稳定缓解患者的诊断效能高于单独使用任何一种,曲线下面积(AUC) 值 0·931。我们的研究结果表明,增加的 ICOS + PD-1 + Tfh细胞与UC发病机制中B细胞的活化有关,可能是UC疾病监测的潜在生物标志物。
更新日期:2020-07-04
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