Vanmaris Remi M M, Rijkers Ger T
Science Department, University College Roosevelt, Middelburg, The Netherlands.
Laboratory for Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands.
Sarcoidosis Vasc Diffuse Lung Dis. 2017;34(2):122-129. doi: 10.36141/svdld.v34i2.5369. Epub 2017 Apr 28.
Sarcoidosis is a systemic inflammatory disease characterized by granulomatous inflammation. The soluble interleukin-2 receptor (sIL-2R) is used as a biomarker for disease severity in sarcoidosis. Moreover, rather than just a biomarker, evidence indicates that sIL-2R could be of biological significance in this disease. The aim of this review is to investigate both its qualities as a biomarker and a potential biological role in sarcoidosis. As a biomarker, the serum level of sIL-2R can be used to distinguish patients from healthy controls, active from inactive disease and to assess treatment success. Additionally, sIL-2R correlates with other biomarkers, including angiotensin-converting enzyme, and with lung function tests and nuclear imaging studies. In sarcoidosis T helper cells and alveolar macrophages are the most likely sources of sIL-2R. While most of the evidence indicates that sIL-2R is generated through proteolytic cleavage of membrane-bound IL-2Rα, no endogenous enzyme has been found to be clearly responsible for sIL-2R formation. It is unclear if sIL-2R has immunostimulatory, immunomodulatory or no functional effects, since conflicting results have been reported. Several potential mechanisms of sIL-2R's biological functions include IL-2 sequestration, prolonging IL-2 half-life, preventing activation of resting T cells or increasing affinity of IL-2Rβ for IL-2. The most likely function of sIL-2R is to modify IL-2 signaling. Increased levels of sIL-2R could either promote disease processes, represent an ineffective attempt to resolve the inflammation or have no effect at all. Further research is required to determine its exact role in the disease and thus its usefulness as a therapeutic target. .
结节病是一种以肉芽肿性炎症为特征的全身性炎症性疾病。可溶性白细胞介素-2受体（sIL-2R）被用作结节病疾病严重程度的生物标志物。此外，有证据表明，sIL-2R在这种疾病中可能具有生物学意义，而不仅仅是一种生物标志物。本综述的目的是研究其作为生物标志物的特性以及在结节病中的潜在生物学作用。作为一种生物标志物，sIL-2R的血清水平可用于区分患者与健康对照、活动期与非活动期疾病，并评估治疗效果。此外，sIL-2R与其他生物标志物相关，包括血管紧张素转换酶，还与肺功能测试和核成像研究相关。在结节病中，辅助性T细胞和肺泡巨噬细胞是sIL-2R最可能的来源。虽然大多数证据表明sIL-2R是通过膜结合IL-2Rα的蛋白水解裂解产生的，但尚未发现明确负责sIL-2R形成的内源性酶。由于报道的结果相互矛盾，尚不清楚sIL-2R是否具有免疫刺激、免疫调节或无功能作用。sIL-2R生物学功能的几种潜在机制包括IL-2隔离、延长IL-2半衰期、防止静息T细胞活化或增加IL-2Rβ对IL-2的亲和力。sIL-2R最可能的功能是修饰IL-2信号传导。sIL-2R水平升高可能促进疾病进程、代表解决炎症的无效尝试或根本没有作用。需要进一步研究以确定其在疾病中的确切作用，从而确定其作为治疗靶点的实用性。
