Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
Department of Respiratory Medicine, Sapporo-Kosei General Hospital, Sapporo, Hokkaido, Japan.
PLoS One. 2020 Nov 2;15(11):e0241719. doi: 10.1371/journal.pone.0241719. eCollection 2020.
Interstitial lung disease (ILD) is a heterogeneous group of diseases characterized by varying degrees of lung inflammation and/or fibrosis. We investigated biomarkers to infer whether patients with collagen vascular diseases associated ILD (CVD-ILD) and interstitial pneumonia with autoimmune features (IPAF) benefit from immunosuppressive therapy.
We retrospectively investigated patients with CVD-ILD, IPAF, and idiopathic pulmonary fibrosis (IPF) between June 2013 and May 2017 at our department. First, we assessed differences in serum and bronchoalveolar lavage fluid (BALF) levels of cytokines between groups. Second, we assessed the associations of patient's clinical variables with serum and BALF levels of those cytokines that were different between groups. Finally, we assessed the associations of diagnosis and response to immunosuppressive therapy with serum levels of those cytokines that were different between groups.
We included 102 patients (51 with IPF, 35 with IPAF, and 16 with CVD-ILD). Serum and BALF levels of CXCL9, CXCL10, and CXCL11 were significantly elevated in patients with IPAF or CVD-ILD compared with those in patients with IPF. BALF levels of CXCL9 and CXCL10 were correlated with the percentages of lymphocytes and macrophages in BALF. Serum levels of CXCL9 and CXCL10 were correlated with BALF levels. Serum levels of CXCL9, CXCL10, and CXCL11 were correlated C-reactive protein, percent predicted forced vital capacity, alveolar-arterial oxygen difference, and the percentages of lymphocytes and macrophages in BALF. Serum levels of CXCL9, CXCL10, and CXCL11 showed moderate accuracy to distinguish patients with CVD-ILD from those with IPAF and IPF. Pre-treatment serum levels of CXCL9 and CXCL11 showed strong positive correlations with the annual forced vital capacity changes in patients with IPAF and CVD-ILD treated with immunosuppressive drugs.
Serum CXCL9, CXCL10, and CXCL11 are potential biomarkers for autoimmune inflammation and predictors of the immunosuppressive therapy responses in ILD with background autoimmunity.
间质性肺疾病（ILD）是一组具有不同程度肺炎症和/或纤维化的异质性疾病。我们研究了生物标志物，以推断胶原血管疾病相关的间质性肺病（CVD-ILD）和具有自身免疫特征的间质性肺炎（IPAF）患者是否受益于免疫抑制治疗。
我们回顾性调查了 2013 年 6 月至 2017 年 5 月在我院就诊的 CVD-ILD、IPAF 和特发性肺纤维化（IPF）患者。首先，我们评估了各组血清和支气管肺泡灌洗液（BALF）中细胞因子水平的差异。其次，我们评估了患者临床变量与组间差异的血清和 BALF 细胞因子水平的相关性。最后，我们评估了诊断和对免疫抑制治疗的反应与组间差异的血清细胞因子水平的相关性。
我们纳入了 102 例患者（51 例 IPF、35 例 IPAF 和 16 例 CVD-ILD）。与 IPF 患者相比，IPAF 或 CVD-ILD 患者的血清和 BALF 中 CXCL9、CXCL10 和 CXCL11 水平显著升高。BALF 中 CXCL9 和 CXCL10 水平与 BALF 中淋巴细胞和巨噬细胞的百分比相关。血清 CXCL9 和 CXCL10 水平与 BALF 水平相关。血清 CXCL9、CXCL10 和 CXCL11 水平与 C 反应蛋白、预计用力肺活量百分比、肺泡-动脉氧差以及 BALF 中淋巴细胞和巨噬细胞的百分比相关。血清 CXCL9、CXCL10 和 CXCL11 水平对区分 CVD-ILD 患者与 IPAF 和 IPF 患者具有中等准确性。治疗前血清 CXCL9 和 CXCL11 水平与 IPAF 和 CVD-ILD 患者接受免疫抑制治疗后用力肺活量的年变化呈强正相关。
血清 CXCL9、CXCL10 和 CXCL11 是自身免疫炎症的潜在生物标志物，也是具有自身免疫背景的 ILD 患者免疫抑制治疗反应的预测因子。
