血清干扰素诱导蛋白评分对系统性硬化症相关间质性肺病治疗反应的预测意义。
Predictive Significance of Serum Interferon-Inducible Protein Score for Response to Treatment in Systemic Sclerosis-Related Interstitial Lung Disease.
机构信息
University of Texas Health Science Center at Houston.
University of California, Los Angeles.
出版信息
Arthritis Rheumatol. 2021 Jun;73(6):1005-1013. doi: 10.1002/art.41627. Epub 2021 Apr 20.
OBJECTIVE
Response to immunosuppression is highly variable in systemic sclerosis (SSc)-related interstitial lung disease (ILD). This study was undertaken to determine whether a composite serum interferon (IFN)-inducible protein score exhibits predictive significance for the response to immunosuppression in SSc-ILD.
METHODS
Serum samples collected in the Scleroderma Lung Study II, a randomized controlled trial of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC), were examined. Results were validated in an independent observational cohort receiving active treatment. A composite score of 6 IFN-inducible proteins IFNγ-inducible 10-kd protein, monokine induced by IFNγ, monocyte chemotactic protein 2, β -microglobulin, tumor necrosis factor receptor type II, and macrophage inflammatory protein 3β) was calculated, and its predictive significance for longitudinal forced vital capacity percent predicted measurements was evaluated.
RESULTS
Higher baseline IFN-inducible protein score predicted better response over 3 to 12 months in the MMF arm (point estimate = 0.41, P = 0.001) and CYC arm (point estimate = 0.91, P = 0.009). In contrast, higher baseline C-reactive protein (CRP) levels were predictive of a worse ILD course in both treatment arms. The predictive significance of the IFN-inducible protein score and CRP levels remained after adjustment for baseline demographic and clinical predictors. During the second year of treatment, in which patients in the CYC arm were switched to placebo, a higher IFN-inducible protein score at 12 months showed a trend toward predicting a worse ILD course (point estimate = -0.61, P = 0.068), while it remained predictive of better response to active immunosuppression in the MMF arm (point estimate = 0.28, P = 0.029). The predictive significance of baseline IFN-inducible protein score was replicated in the independent cohort (r = 0.43, P = 0.028).
CONCLUSION
A higher IFN-inducible protein score in SSc-ILD is predictive of better response to immunosuppression and could potentially be used to identify patients who may derive the most benefit from MMF or CYC.
目的
系统性硬皮病（SSc）相关间质性肺病（ILD）患者对免疫抑制的反应差异很大。本研究旨在确定血清干扰素（IFN）诱导蛋白评分是否对 SSc-ILD 患者对免疫抑制的反应具有预测意义。
方法
检测了 Scleroderma Lung Study II 中收集的血清样本，这是一项霉酚酸酯（MMF）与环磷酰胺（CYC）对照的随机临床试验。结果在接受积极治疗的独立观察队列中得到了验证。计算了 6 种 IFN 诱导蛋白（IFNγ诱导的 10-kd 蛋白、IFNγ诱导的单核细胞因子、单核细胞趋化蛋白 2、β-微球蛋白、肿瘤坏死因子受体 II 和巨噬细胞炎症蛋白 3β）的复合评分，并评估了其对纵向用力肺活量预测百分比测量的预测意义。
结果
MMF 组（估计点=0.41，P=0.001）和 CYC 组（估计点=0.91，P=0.009）中较高的基线 IFN 诱导蛋白评分预示着治疗 3 至 12 个月时的反应更好。相比之下，较高的基线 C 反应蛋白（CRP）水平在两种治疗组中均预示着 ILD 病情更差。调整基线人口统计学和临床预测因素后，IFN 诱导蛋白评分和 CRP 水平的预测意义仍然存在。在 CYC 组的第二年，即患者转换为安慰剂时，12 个月时较高的 IFN 诱导蛋白评分显示出预测 ILD 病情恶化的趋势（估计点=-0.61，P=0.068），而在 MMF 组中，它仍然预示着对活性免疫抑制的反应更好（估计点=0.28，P=0.029）。在独立队列中，也复制了基线 IFN 诱导蛋白评分的预测意义（r=0.43，P=0.028）。
结论
SSc-ILD 中较高的 IFN 诱导蛋白评分预示着对免疫抑制的反应更好，可能有助于识别从 MMF 或 CYC 中获益最大的患者。
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