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Correlation of peripheral CD4+GranzB+CTLs with disease severity in patients with primary Sjögren’s syndrome
Arthritis Research & Therapy ( IF 4.4 ) Pub Date : 2021-10-12 , DOI: 10.1186/s13075-021-02632-6
Qi Wang 1 , Nan Che 1 , Chengyin Lu 1 , Xiaoxuan Sun 1 , Yanyan Wang 1 , Qiang Wang 1 , Wenfeng Tan 1 , Lanlan Zhou 1 , Xiaojun Zhang 1 , Dong Xu 2 , Lei Gu 1 , Miaojia Zhang 1
Affiliation  

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease which has focal lymphocytic infiltration including a majority of CD4+ T cells. This study was to investigate the correlation of peripheral granzyme B (GranzB)-expressing CD4+ T cells with disease severity and histological lesion in patients with pSS. We recruited 116 pSS and 46 health control (HC) using flow cytometry to examine the percentage of CD4+GranzB+CTLs in the peripheral blood, and immunofluorescence to test their expression in the labial gland. The percentage of CD4+GranzB+CTLs was significantly upregulated in pSS than in HC (7.1 ± 4.9% vs 3.1 ± 1.9%, p < 0.0001) and positive correlation with ESSDAI. The frequency of them was markedly higher in pSS with extraglandular manifestations. After excluding the other risk factors associated with pSS, they were still related to ESSDIA and extraglandular manifestations independently (p < 0.05), and they are the risk factor of extraglandular involvement (odds ratio = 1.928). Moreover, they could be observed in the LSGs. ROC curve analysis indicated that the area under the curve (AUC) of CD4+GranzB+CTLs was 0.796 to predict the activity of pSS and 0.851 to presume extraglandular manifestations. The best diagnostic cutoff point was 4.865 for pSS patients. In this study, we provide new evidence indicating the involvement of CD4+GranzB+CTLs over activation in the pathophysiology of pSS, which may serve as a new biomarker to evaluate the activity and severity of pSS.

中文翻译:

原发性干燥综合征患者外周 CD4+GranzB+CTLs 与疾病严重程度的相关性

原发性干燥综合征 (pSS) 是一种慢性全身性自身免疫性疾病,具有包括大部分 CD4+ T 细胞在内的局灶性淋巴细胞浸润。本研究旨在探讨表达外周颗粒酶 B (GranzB) 的 CD4+ T 细胞与 pSS 患者疾病严重程度和组织学病变的相关性。我们招募了 116 名 pSS 和 46 名健康控制 (HC),使用流式细胞术检查外周血中 CD4+GranzB+CTL 的百分比,并使用免疫荧光检测它们在唇腺中的表达。与 HC 相比,pSS 中 CD4+GranzB+CTL 的百分比显着上调(7.1 ± 4.9% vs 3.1 ± 1.9%,p < 0.0001),并且与 ESSDAI 呈正相关。在具有腺外表现的 pSS 中,它们的频率明显更高。在排除与 pSS 相关的其他风险因素后,它们仍与 ESSDIA 和腺外表现独立相关(p < 0.05),它们是腺外受累的危险因素(比值比 = 1.928)。此外,它们可以在 LSG 中观察到。ROC 曲线分析表明,CD4+GranzB+CTLs 的曲线下面积(AUC)为 0.796 可预测 pSS 的活性,0.851 可预测腺外表现。pSS 患者的最佳诊断截止点为 4.865。在这项研究中,我们提供了新的证据表明 CD4+GranzB+CTLs 过度激活参与了 pSS 的病理生理学,这可能作为评估 pSS 活性和严重程度的新生物标志物。它们可以在 LSG 中观察到。ROC 曲线分析表明,CD4+GranzB+CTLs 的曲线下面积(AUC)为 0.796 可预测 pSS 的活性,0.851 可预测腺外表现。pSS 患者的最佳诊断截止点为 4.865。在这项研究中,我们提供了新的证据表明 CD4+GranzB+CTLs 过度激活参与了 pSS 的病理生理学,这可能作为评估 pSS 活性和严重程度的新生物标志物。它们可以在 LSG 中观察到。ROC 曲线分析表明,CD4+GranzB+CTLs 的曲线下面积(AUC)为 0.796 可预测 pSS 的活性,0.851 可预测腺外表现。pSS 患者的最佳诊断截止点为 4.865。在这项研究中,我们提供了新的证据表明 CD4+GranzB+CTLs 过度激活参与了 pSS 的病理生理学,这可能作为评估 pSS 活性和严重程度的新生物标志物。
更新日期:2021-10-12
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