DataSheet_1_FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis.docx

RationaleSarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to evaluate the association of disease course and immune responses in pulmonary sarcoidosis.
MethodsIn this prospective cohort study of 30 subjects, most of whom were followed for one year, we evaluated 14 inflammatory markers in plasma, 13 Treg/T cell flow cytometry markers and 8 parameters of FOXP3+ Treg biology, including suppressive function, epigenetic features and stability.
ResultsWe identified a set of 13 immunological parameters that differ in sarcoidosis subjects in comparison with healthy donors. Five of those were inversely correlated with suppressive function of Tregs in sarcoidosis, and six (TNFα, TNFR I and II, sCD25, Ki-67 and number of Tregs) were particularly upregulated or increased in subjects with thoracic lymphadenopathy. Treg suppressive function was significantly lower in patients with thoracic lymphadenopathy, and in patients with higher burdens of pulmonary and systemic symptoms. A combination of five inflammatory markers, Ki-67 expression, Treg function, and lung diffusion capacity evaluated at study entry predicted need for therapy at one year follow-up in 90% of cases.
ConclusionTregs may suppress ongoing inflammation at local and systemic levels, and TNFα, TNFR I and II, sCD25 and Ki-67 emerge as attractive biomarkers for in vivo sarcoid inflammatory activity.

研究背景（Rationale）：结节病（Sarcoidosis）是一种病因未明的炎症性肉芽肿性疾病，以肺部受累为主要表现。患者的器官受累情况、疾病严重程度以及免疫改变的特征存在个体差异，由此产生了多样的临床表型与转归。本研究旨在评估肺结节病（pulmonary Sarcoidosis）患者的疾病进程与免疫应答之间的关联。
方法：本研究为一项纳入30名受试者的前瞻性队列研究，其中多数受试者接受了为期1年的随访。研究人员对受试者血浆中的14种炎症标志物、13种Treg/T细胞流式细胞术（flow cytometry）标志物以及8项FOXP3+调节性T细胞（FOXP3+ Treg）生物学参数进行了检测，涵盖抑制功能、表观遗传特征与细胞稳定性三个方面。
结果：本研究鉴定出13项免疫参数在结节病患者与健康供者间存在显著差异。其中5项参数与结节病患者的Treg抑制功能呈负相关；另有6项指标——肿瘤坏死因子α（TNFα）、肿瘤坏死因子受体I/II（TNFR I/II）、可溶性CD25（sCD25）、Ki-67以及Treg细胞数量，在伴有胸腔淋巴结病的患者中显著上调或升高。伴有胸腔淋巴结病的患者，以及肺与全身症状负荷更高的患者，其Treg抑制功能显著降低。在研究入组时检测的5种炎症标志物组合、Ki-67表达水平、Treg功能以及肺弥散功能（lung diffusion capacity），可在90%的受试病例中预测1年随访期内的治疗需求。
结论：Treg可在局部与全身层面抑制持续存在的炎症反应，而TNFα、TNFR I/II、sCD25及Ki-67可作为评估结节病体内炎症活性的极具潜力的生物标志物。