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.
- paediatric interstitial lung disease
- rare lung diseases
- systemic disease and lungs
- massive haemoptysis
- paediatric lung disaese
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Contributors M-LF performed the functional studies under the direction of YC; NN was in charge of the patient and the treatment monitoring in the Reference Center headed by AC. ML and NN were responsible for the genetic studies under the direction of SA. SR, MF, LB, NR, BN participated in the care of the patient. CS, HDLP, AC, HB reviewed the imaging and histological data. GIR, DD and VB participated in the functional studies. M-LF and NN wrote the manuscript, which was reviewed by all of the authors.
Funding Our work is supported by grants from the Institut National de la Santé et la Recherche Médicale (Inserm, reference: 000427993 for M-LF), the Legs Poix from the Chancellerie des Universités (grants 2013 n°1305, 2014 n°1405, 2015 n°1015, 2016 n°2077 and 2017 n°DP2017/1860), Paris, the European Union’s Seventh Framework Program (FP7-ChILD-EU 2007-2013) under grant agreement n°305653, as well as funding from the patient organisations 'Respirer c’est Grandir' and 'Belleherbe Association'.
Competing interests None declared.
Patient consent for publication Parental/guardian consent obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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