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Case based discussion
Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage
  1. Marie-Louise Frémond1,
  2. Marie Legendre2,3,
  3. Michael Fayon4,
  4. Annick Clement2,5,
  5. Emilie Filhol-Blin2,
  6. Nicolas Richard5,
  7. Laura Berdah5,
  8. Sylvie Roullaud6,
  9. Gillian I Rice7,
  10. Vincent Bondet8,
  11. Darragh Duffy8,
  12. Chiara Sileo9,
  13. Hubert Ducou le Pointe9,
  14. Hugues Begueret10,
  15. Aurore Coulomb11,
  16. Bénédicte Neven12,13,
  17. Serge Amselem2,
  18. Yanick Crow1,14,
  19. Nadia Nathan2,5
  1. 1 Laboratory of Neurogenetics and Neuroinflammation, Paris Descartes University, Sorbonne-Paris-Cité, Imagine Institute, Paris, France
  2. 2 Inserm UMR_S933, INSERM and Sorbonne Université, Paris, France
  3. 3 Molecular Genetic Department, APHP, Trousseau Hospital, Sorbonne Université, Paris, France
  4. 4 Pediatric Pulmonology & CIC 1401, Cardio-Thoracic Research Center (U1045), Bordeaux University Hospital, Bordeaux, France
  5. 5 Pediatric Pulmonology and Reference centre for rare lung diseases, AP-HP, Trousseau Hospital, Sorbonne University, Paris, France
  6. 6 Pediatric Department, CH Angouleme, Angouleme, Poitou-Charentes, France
  7. 7 Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
  8. 8 Inserm 1223, and Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France
  9. 9 Imaging Department, AP-HP, Trousseau Hospital, Sorbonne University, Paris, France
  10. 10 Pathology Department, Haut Lévêque University Hospital, Pessac, France
  11. 11 Pathology Department, APHP, Hôpital Trousseau, Sorbonne Université, Paris, France
  12. 12 Inserm UMR 1163, Laboratory of Immunogenetics of Pediatric Autoimmunity, Paris Descartes University, Sorbonne-Paris-Cité, Paris, France
  13. 13 Paediatric Hematology-Immunology and Rheumatology Department, APHP, Necker Enfants Malades Hospital, Paris, France
  14. 14 Centre for Genomic and Experimental Medicine, The University of Edinburgh MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK
  1. Correspondence to Dr Nadia Nathan, Pediatric Pulmonology and Reference centre for rare lung diseases, AP-HP, Trousseau Hospital, Sorbonne University, Paris 75012, France; nadia.nathan{at}


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.