Clinical Pathology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Rheumatology Section, Department of Internal Medicine, University of Palermo, Palermo, Italy.
Arthritis Res Ther. 2020 Jun 1;22(1):127. doi: 10.1186/s13075-020-02218-8.
Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with a progressive elevation in pulmonary vascular resistance and subsequent right heart failure and death. Due to unspecific symptoms, the diagnosis of PAH is often delayed. On this basis, it is of great value to improve current diagnostic methods and develop new strategies for evaluating patients with suspected PAH. Interleukin-32 (IL-32) is a proinflammatory cytokine expressed in damaged vascular cells, and the present study aimed to assess if this cytokine could be a new biomarker of PAH during SSc.
The IL-32 expression was evaluated in the sera and skin samples of 18 SSc-PAH patients, 21 SSc patients without PAH, 15 patients with idiopathic PAH (iPAH) and 14 healthy controls (HCs), by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). Receiver-operating characteristic (ROC) curves were performed to evaluate the cut-off of IL-32 in identifying patients with PAH. Furthermore, in SSc patients, correlation analyses were performed between IL-32 sera levels and mean pulmonary artery pressure (mPAP) evaluated by right heart catheterization (RHC) and systolic pulmonary artery pressure (sPAP), obtained by echocardiography. Additionally, the number of skin IL-32+ cells was correlated with modified Rodnan skin score (mRSS).
In SSc-PAH patients, IL-32 sera levels were significantly higher when compared with SSc patients without PAH and patients affected by iPAH. The analysis of ROC curve showed that IL-32 sera levels above 11.12 pg/ml were able to predict patients with PAH (sensitivity = 90%, specificity = 100%). Furthermore, the IL-32 sera levels of patients with SSc correlated with both mPAP and sPAP. In the skin derived from SSc-PAH patients, the number of IL-32+ cells was significantly increased when compared with the skin derived from SSc patients without PAH, correlating with the mRSS.
Our study suggested that sera determination of IL-32 may be a promising approach to evaluate the presence of PAH in SSc patients and together with longitudinal future studies could help to increase the understanding how these biomarkers mirror the vascular changes and the inflammatory process during SSc.
肺动脉高压（PAH）是系统性硬化症（SSc）的严重并发症，与肺血管阻力的进行性升高以及随后的右心衰竭和死亡有关。由于症状不特异，PAH 的诊断常常被延误。在此基础上，提高现有诊断方法并开发新的策略来评估疑似 PAH 患者具有重要意义。白细胞介素 32（IL-32）是一种在受损血管细胞中表达的促炎细胞因子，本研究旨在评估这种细胞因子是否可作为 SSc 中 PAH 的新生物标志物。
采用酶联免疫吸附试验（ELISA）和免疫组织化学（IHC）检测 18 例 SSc-PAH 患者、21 例 SSc 无 PAH 患者、15 例特发性 PAH（iPAH）患者和 14 名健康对照者（HCs）的血清和皮肤样本中的 IL-32 表达。通过绘制受试者工作特征（ROC）曲线评估 IL-32 在识别 PAH 患者中的截断值。此外，在 SSc 患者中，还分析了血清 IL-32 水平与右心导管（RHC）评估的平均肺动脉压（mPAP）和超声心动图检测的收缩期肺动脉压（sPAP）之间的相关性。另外，还分析了皮肤 IL-32+细胞数量与改良 Rodnan 皮肤评分（mRSS）之间的相关性。
与 SSc 无 PAH 患者和 iPAH 患者相比，SSc-PAH 患者的血清 IL-32 水平明显升高。ROC 曲线分析表明，血清 IL-32 水平高于 11.12 pg/ml 时能够预测 PAH 患者（敏感性=90%，特异性=100%）。此外，SSc 患者的血清 IL-32 水平与 mPAP 和 sPAP 均相关。与 SSc 无 PAH 患者相比，SSc-PAH 患者皮肤中的 IL-32+细胞数量显著增加，且与 mRSS 相关。
本研究表明，血清 IL-32 测定可能是评估 SSc 患者 PAH 存在的一种有前途的方法，结合未来的纵向研究有助于增加对这些生物标志物如何反映 SSc 期间血管变化和炎症过程的理解。
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