COPA (coatomer subunit α) syndrome is a newly recognised cause of interstitial lung disease in children and adults, frequently associated with arthritis and renal dysfunction. We report a 11-year-old girl with disease limited to major pulmonary haemosiderosis manifesting at the age of 2 years, due to a heterozygous p.(Arg233His) mutation in COPA. Her interferon (IFN) signature was elevated (10.312 and 12.429, healthy <2.466), as was the level of serum IFNα (211 fg/mL, healthy <10 fg/mL). STAT1 phosphorylation in T lymphocytes and monocytes was increased as compared with healthy controls. Based on these results she was treated with the JAK1/2 inhibitor ruxolitinib, which resulted in reduction in IFN signalling and appeared to be associated with partial though incomplete decrease in the severity of her pulmonary disease. Patients with alveolar haemorrhage of unknown origin should be considered for COPA screening. Functional tests can help to personalise patient therapy.

中文翻译：

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鲁索替尼在表现为危及生命的肺泡出血的 COPA 综合征中的应用


COPA（涂层亚基 α）综合征是儿童和成人间质性肺疾病的新发现原因，通常与关节炎和肾功能障碍相关。我们报告了一名 11 岁女孩，由于 COPA 中的 p.(Arg233His) 杂合突变，其疾病仅限于 2 岁时出现的严重肺含铁血黄素沉着症。她的干扰素 (IFN) 特征升高（10.312 和 12.429，健康 <2.466），血清 IFNα 水平​​也升高（211 fg/mL，健康 <10 fg/mL）。与健康对照相比，T 淋巴细胞和单核细胞中的 STAT1 磷酸化增加。根据这些结果，她接受了 JAK1/2 抑制剂鲁索替尼治疗，这导致 IFN 信号传导减少，并且似乎与她的肺部疾病严重程度部分但不完全降低有关。不明原因肺泡出血的患者应考虑进行 COPA 筛查。功能测试有助于个性化患者治疗。