■结节病是一种病因不明的炎性肉芽肿性疾病,主要累及肺部。器官受累和疾病严重程度,以及免疫改变的性质,不同的患者导致一系列的临床表型和结局.我们的目的是评估肺结节病的病程和免疫反应的关系。
■在这项30名受试者的前瞻性队列研究中,大多数人被跟踪了一年,我们评估了血浆中的14种炎症标志物,13个Treg/T细胞流式细胞术标志物和FOXP3+Treg生物学的8个参数,包括抑制功能,表观遗传特征和稳定性。
■我们确定了一组13个免疫学参数,这些参数在结节病受试者中与健康供体相比有所不同。其中5例与结节病中Tregs的抑制功能呈负相关,和六个(TNFα,TNFRI和II,在患有胸淋巴结病的受试者中,sCD25,Ki-67和Tregs的数量)特别上调或增加。胸淋巴结病患者的Treg抑制功能明显降低,以及肺部和全身症状负担较高的患者。五种炎症标志物的组合,Ki-67表达,Treg功能,进入研究时评估的肺弥散能力预测了90%病例在1年随访时需要治疗。
■Tregs可以抑制局部和全身水平的持续炎症,和TNFα,TNFRI和II,sCD25和Ki-67是体内类肉瘤炎症活性的有吸引力的生物标志物。
Sarcoidosis 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.
In 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.
We 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.
Tregs 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.