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原发性和继发性干燥综合征患者细胞因子表达差异及调节性细胞

Differential cytokine expression and regulatory cells in patients with primary and secondary Sjögren's syndrome.

作者信息

Furuzawa-Carballeda J, Sánchez-Guerrero J, Betanzos J L, Enriquez A B, Avila-Casado C, Llorente L, Hernández-Molina G

机构信息

Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

出版信息

Scand J Immunol. 2014 Dec;80(6):432-40. doi: 10.1111/sji.12224.

DOI:10.1111/sji.12224
PMID:25346207
Abstract

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands. The aim of the study was to characterize and compare the presence of diverse cytokines and regulatory T and B cells in lip minor salivary gland (MSG) biopsies from patients with primary Sjögren's syndrome (pSS), secondary SS (sSS), and patients with connective tissue disease (CTD) without (w/o) SS. We included samples of MSG from 15 pSS, 24 sSS (six scleroderma, nine rheumatoid arthritis and nine lupus patients) and 15 patients with CTD w/o SS. Tissues were examined by an indirect immunoperoxidase technique (goat polyclonal anti-human IL-19, goat polyclonal anti-human IL-22 or mouse monoclonal anti-human IL-24). To determine the subpopulation of CD4(+)/IL-17A(+)-, CD4(+)/IL-4(+)-, CD4(+)/IFN-ɣ(+)-expressing T cells, CD25(+)/Foxp3(+) Treg cells and CD20(+)/IL-10(+)-producing B cell subset, a double-staining procedure was performed. We estimated the mean percentage of positively staining cells in two fields per sample. CD4(+)/IFN-ɣ(+), CD4(+)/IL-4(+) and IL-22(+) cell percentages were elevated in both SS varieties; however, the cells were more prevalent in pSS. Patients with pSS had a high number of CD4(+)/IL-17A(+) and IL-19(+) T cells and a lower percentage of IL-24(+) cells (P < 0.05). The Treg and IL-10-producing B cells were increased in pSS (P < 0.05). Concluding, in our patients, a pro-inflammatory and regulatory balance coexists in SS, being both responses more intense in pSS. The explanation of these differences may be related to disease activity, disease duration and treatment.

摘要

干燥综合征(SS)是一种自身免疫性疾病,其特征为唾液腺和泪腺的淋巴细胞浸润。本研究的目的是对原发性干燥综合征(pSS)、继发性干燥综合征(sSS)以及无干燥综合征(w/o)的结缔组织病(CTD)患者的唇部小唾液腺(MSG)活检中多种细胞因子以及调节性T细胞和B细胞的存在情况进行表征和比较。我们纳入了15例pSS、24例sSS(6例硬皮病、9例类风湿关节炎和9例狼疮患者)以及15例无干燥综合征的CTD患者的MSG样本。通过间接免疫过氧化物酶技术(山羊多克隆抗人IL-19、山羊多克隆抗人IL-22或小鼠单克隆抗人IL-24)对组织进行检测。为了确定表达CD4(+)/IL-17A(+)、CD4(+)/IL-4(+)、CD4(+)/IFN-ɣ(+)的T细胞亚群、CD25(+)/Foxp3(+)调节性T细胞以及产生CD20(+)/IL-10(+)的B细胞亚群,进行了双重染色程序。我们估计了每个样本两个视野中阳性染色细胞的平均百分比。在两种干燥综合征类型中,CD4(+)/IFN-ɣ(+)、CD4(+)/IL-4(+)和IL-22(+)细胞百分比均升高;然而,这些细胞在pSS中更为普遍。pSS患者有大量的CD4(+)/IL-17A(+)和IL-19(+) T细胞,而IL-24(+)细胞的百分比更低(P < 0.05)。pSS中调节性T细胞和产生IL-10的B细胞增加(P < 0.05)。总之,在我们的患者中,干燥综合征存在促炎和调节平衡,且两种反应在pSS中更为强烈。这些差异的解释可能与疾病活动度、病程和治疗有关。

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