Circulating CTRP9 Is Associated With Severity of Systemic Sclerosis-Associated Interstitial Lung Disease.
Circulating CTRP9 Is Associated With Severity of Systemic Sclerosis-Associated Interstitial Lung Disease.
复制标题
DOI：
10.1002/acr.24749
复制
发表时间：
2023-01
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
虽然间质性肺疾病 (ILD) 是系统性硬化症 (SSc) 发病和死亡的主要原因，但评估疾病进展的预测标记物仍然很少。我们之前证明，SSc 中脂肪组织代谢和脂肪因子稳态失调。我们试图确定新型脂肪因子 C1q/TNF 相关蛋白 9 (CTRP9) 对 SSc-ILD 的关联和预测能力。我们利用西北硬皮病计划患者登记和生物样本库进行了一项回顾性纵向研究。在基线时测量了 110 名 SSc 患者的 CTRP9 血清水平，并每隔 12 个月至 48 个月收集人口统计、临床和肺功能测试数据。预测用力肺活量百分比 (FVC%) 的纵向轨迹被用作主要结果指标。我们利用混合模型来比较 CTRP9 组的肺功能轨迹，并进行潜在轨迹分析以适应异质性。在横断面分析中，循环 CTRP9 升高与基线时（72%±17 vs. 80%±18，p=0.02）和 48 个月（68±19 vs. 84±18，p=0.001）显着降低的 FVC% 相关。在混合模型分析中，高 CTRP9 与较差的肺功能相关，但与不同的轨迹无关 (p=0.23)。相比之下，低 CTRP9 可以以合理的准确度（敏感性 = 73%）识别肺部疾病稳定的患者。潜在轨迹分析证实了较低的 CTRP9 与较高的 FVC% 之间的关联。较高的循环 CTRP9 与较差的肺功能相关，而较低的 CTRP9 则表明患者随着时间的推移肺部疾病的稳定性。这些发现表明 CTRP9 可能是 SSc 相关 ILD 的潜在生物标志物。
While interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc), there remains a paucity of predictive markers to assess disease progression. We previously demonstrated that adipose tissue metabolism and adipokine homeostasis is dysregulated in SSc. We sought to determine the association and predictive ability of the novel adipokine C1q/TNF-Related Protein 9 (CTRP9) for SSc-ILD. We performed a retrospective longitudinal study utilizing the Northwestern Scleroderma Program Patient Registry and Biorepository. Serum levels of CTRP9 were measured in 110 SSc patients at baseline, and demographic, clinical and pulmonary function test data were collected in 12-month intervals to 48 months. Longitudinal trajectory of forced vital capacity percent predicted (FVC%) was used as a primary outcome measure. We utilized a mixed model to compare trajectories of lung function by CTRP9 groups and performed latent trajectory analysis to accommodate for heterogeneity. In cross-sectional analysis, elevated circulating CTRP9 was associated with significantly lower FVC% at baseline (72%±17 vs. 80%±18, p=0.02) and 48 months (68±19 vs. 84±18, p=0.001). In mixed model analysis, high CTRP9 was associated with worse lung function, but not with a different trajectory (p=0.23). In contrast, low CTRP9 identified patients with stability of lung disease with reasonable accuracy (sensitivity=73%). Latent trajectory analysis confirmed the association of lower CTRP9 with higher FVC%. Higher circulating CTRP9 associated with worse pulmonary function while low CTRP9 identified patients with lung disease stability over time. These findings suggest that CTRP9 may be a potential biomarker in SSc-associated ILD.