Qian Junyan, Ding Yufang, Yang Xiaoxi, Wang Qian, Zhao Jiuliang, Liu Yongtai, Tian Zhuang, Wang Yanhong, Li Mengtao, Zeng Xiaofeng
Department of Rheumatology and Clinical Immunology, State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Peking Union Medical College Hospital (PUMCH), Peking Union Medical College & Chinese Academy of Medical Sciences Ministry of Education Beijing China.
Class 2017, China Academy of Medical Sciences and Peking Union Medical College Beijing China.
Pulm Circ. 2023 Feb 10;13(1):e12195. doi: 10.1002/pul2.12195. eCollection 2023 Jan.
Growth-differentiation factor (GDF)-15 is a member of transforming growth factor-β-related cytokine and may respond to right ventricular overload. The objective of this article was to assess the diagnosis and prognostic value of GDF-15 in systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). Serum samples were obtained from 65 patients with SLE-PAH, 51 sex and age matched patients of SLE without PAH (SLE-non-PAH), and 32 healthy controls. Serum GDF-15 level was detected by enzyme-linked immunosorbent assay and the optimal cut-off point was determined by receiver operating characteristic curve. The primary end-point was death from any cause and the secondary end-point was target goal achievement (TGA). Cox regression analyses and Kaplan-Meier method were performed to identify the prognostic value of GDF-15. Serum GDF-15 levels were significantly higher in SLE-PAH patients (1112.14 ± 781.80 pg/mL) than SLE-non-PAH patients (810 ± 408 pg/mL) and healthy controls (442 ± 139 pg/mL) at baseline. The optimal cut-off value of GDF-15 in the diagnosis of SLE-PAH was 733 pg/mL (AUC = 0.84). In patients with SLE-PAH, GDF-15 level was associated with 6 min walking distance ( = -0.385, = 0.017) and higher serum N terminal-pro brain natriuretic peptide (NT-proBNP) ( = 0.605, < 0.001). Patients with GDF-15 > 733 pg/mL were more likely to death (adjusted hazard ratio [HR] = 4.01, 95% confidence intervals [CI]: 1.23-6.27, = 0.041) and less likely to achieve treatment goal (adjusted HR = 0.57, 95% CI: 0.23-0.79, = 0.028). In addition, patients with simultaneous elevation of GDF-15 and NT-proBNP showed lower proportion of TGA ( = 0.046). In conclusion, GDF-15 is a new and promising biomarker of development and prognosis in SLE-PAH. The combination of GDF-15 and NT-proBNP may provide more accurate prognostic information.
生长分化因子（GDF）-15是转化生长因子-β相关细胞因子的成员之一，可能对右心室负荷过重产生反应。本文的目的是评估GDF-15在系统性红斑狼疮相关肺动脉高压（SLE-PAH）中的诊断和预后价值。收集了65例SLE-PAH患者、51例年龄和性别匹配的无PAH的SLE患者（SLE-非PAH）以及32名健康对照者的血清样本。采用酶联免疫吸附测定法检测血清GDF-15水平，并通过受试者工作特征曲线确定最佳截断点。主要终点是任何原因导致的死亡，次要终点是达到目标治疗效果（TGA）。进行Cox回归分析和Kaplan-Meier法以确定GDF-15的预后价值。在基线时，SLE-PAH患者的血清GDF-15水平（1112.14±781.80 pg/mL）显著高于SLE-非PAH患者（810±408 pg/mL）和健康对照者（442±139 pg/mL）。GDF-15诊断SLE-PAH的最佳截断值为733 pg/mL（AUC = 0.84）。在SLE-PAH患者中，GDF-15水平与6分钟步行距离相关（r = -0.385，P = 0.017），且与较高的血清N末端脑钠肽前体（NT-proBNP）相关（r = 0.605，P < 0.001）。GDF-15>733 pg/mL的患者死亡可能性更高（校正风险比[HR] = 4.01，95%置信区间[CI]：1.23 - 6.27，P = 0.041），达到治疗目标的可能性更低（校正HR = 0.57，95%CI：0.23 - 0.79，P = 0.028）。此外，GDF-15和NT-proBNP同时升高的患者TGA比例较低（P = 0.046）。总之，GDF-15是SLE-PAH发生发展和预后的一种新的、有前景的生物标志物。GDF-15与NT-proBNP联合使用可能提供更准确的预后信息。
