Malkova Anna, Zinchenko Yulia, Starshinova Anna, Kudlay Dmitriy, Kudryavtsev Igor, Glushkova Anzhela, Yablonskiy Piotr, Shoenfeld Yehuda
Laboratory of the Mosaic of Autoimmunity, St. Petersburg State University, Saint Petersburg, Russia.
Phthisiopulmonology Department, St. Petersburg Research Institute of Phthisiopulmonology, Saint Petersburg, Russia.
Front Med (Lausanne). 2022 Sep 6;9:963435. doi: 10.3389/fmed.2022.963435. eCollection 2022.
Many factors confirm the autoimmune nature of sarcoidosis and help in determining the strategy of patient management and treatment initiation. However, the causes and the mechanisms of disease progression that result in fibrosis and insufficiency of the affected organ remain unclear. This narrative review aims to analyse the mechanisms and biomarkers of sarcoidosis progression, as well as the pathogenetic basis of sarcoidosis therapy. The following characteristics of progressive chronic sarcoidosis were revealed: the disease develops in patients with a genetic predisposition (SNP in genes GREM1, CARD15, TGF-β3, HLA-DQB106:02, HLA-DRB107/14/15), which contributes either the decreased ability of antigen elimination or autoimmune inflammation. Various prognostic biomarkers of disease progression (decreased levels of neopterin, elastase, sIL-2R, chitotriosidase, glycoprotein Krebs von den Lungen, Th17 cell count, reduced quantity of TNF-α in peripheral blood or bronchoalveolar lavage fluid) have been described and can potentially be used to determine the group of patients who will benefit from the use of corticosteroids/cytostatic drugs/biologics.
许多因素证实了结节病的自身免疫性质,并有助于确定患者管理和治疗启动策略。然而,导致受影响器官纤维化和功能不全的疾病进展原因及机制仍不清楚。本叙述性综述旨在分析结节病进展的机制和生物标志物,以及结节病治疗的发病基础。揭示了进行性慢性结节病的以下特征:该疾病在具有遗传易感性(GREM1、CARD15、TGF-β3、HLA-DQB106:02、HLA-DRB107/14/15基因中的单核苷酸多态性)的患者中发生,这导致抗原清除能力下降或自身免疫炎症。已描述了疾病进展的各种预后生物标志物(新蝶呤、弹性蛋白酶、可溶性白细胞介素-2受体、壳三糖苷酶、肺克雷伯糖蛋白水平降低,Th17细胞计数、外周血或支气管肺泡灌洗液中TNF-α数量减少),它们有可能用于确定将从使用皮质类固醇/细胞毒性药物/生物制剂中获益的患者群体。