Ometto Francesca, Friso Lara, Astorri Davide, Botsios Costantino, Raffeiner Bernd, Punzi Leonardo, Doria Andrea
Medicine Department - DIMED, Rheumatology Unit, University of Padova, Padova 35128, Italy.
Exp Biol Med (Maywood). 2017 Apr;242(8):859-873. doi: 10.1177/1535370216681551. Epub 2016 Jan 1.
Calprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-α inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker. Impact statement Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment.
钙卫蛋白是一种由两种蛋白质S100A8和S100A9形成的异二聚体,它们主要由循环系统和炎症组织中活化的单核细胞和中性粒细胞产生。钙卫蛋白在炎症过程中的作用已经得到证实,但近年来其在风湿性疾病的发病机制、诊断和监测中的作用受到了极大关注。钙卫蛋白在室温下稳定,是许多自身免疫性疾病疾病活动随访的候选生物标志物,它可以预测对治疗的反应或疾病复发。有证据表明,包括肿瘤坏死因子-α抑制剂在内的多种免疫调节剂可能会降低钙卫蛋白的表达。在自身免疫性疾病的小鼠模型中,S100A8和S100A9作为治疗靶点具有潜在作用,因为直接或间接阻断这些蛋白质会改善疾病进程。在这篇综述中,我们将探讨可能参与风湿性疾病病因的钙卫蛋白的生物学功能。我们还将报告其作为疾病生物标志物潜在用途的证据。影响声明钙卫蛋白是循环系统和炎症组织中单核细胞和中性粒细胞产生的一种急性期蛋白。钙卫蛋白似乎比CRP更敏感,能够检测到最小程度的残留炎症,是炎症性疾病的候选生物标志物。高血清水平与风湿性疾病的一些严重表现有关,如肾小球肾炎和肺纤维化。唾液和滑液等其他体液中的钙卫蛋白水平可能有助于风湿性疾病的诊断。钙卫蛋白作为治疗靶点的潜在作用也很有趣。