Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage

Marie-Louise Frémond (1) , Marie Legendre (2, 3, 4) , Michael Fayon (5) , Annick Clement (3, 2, 6) , Emilie Filhol-Blin (3) , Nicolas Richard (2) , Laura Berdah (2) , Sylvie Roullaud (7) , Gillian Rice (8) , Vincent Bondet (9) , Darragh Duffy (9) , Chiara Sileo (10) , Hubert Ducou Le Pointe (10) , Hugues Begueret (11) , Aurore Coulomb (2) , Bénédicte Neven (1, 12) , Serge Amselem (3, 4) , Yanick Crow (1, 13) , Nadia Nathan (14, 3)

1 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
2 CHU Trousseau [APHP]
3 Inserm U933 - Maladies génétiques d'expression pédiatrique [CHU Trousseau]
4 UF de Génétique moléculaire [CHU Trousseau]
5 CRCTB - Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux]
6 Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau]
7 CH Angoulême - Centre Hospitalier d'Angoulême
8 MAHSC - Manchester Academic Health Science Centre
9 Immunobiologie des Cellules dendritiques
10 Service de Radiologie [CHU Trousseau]
11 Hôpital Haut-Lévêque [CHU Bordeaux]
12 CHU Necker - Enfants Malades [AP-HP]
13 University of Edinburgh
14 Service de Pneumologie pédiatrique [CHU Trousseau]

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.

Keywords: rare lung diseases; paediatric lung disaese; systemic disease and lungs; massive haemoptysis; paediatric interstitial lung disease

Domains: Immunology

Marie-Louise Frémond, Marie Legendre, Michael Fayon, Annick Clement, Emilie Filhol-Blin, et al.. Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage. Thorax, 2019, pp.thoraxjnl-2019-213892. ⟨10.1136/thoraxjnl-2019-213892⟩. ⟨pasteur-02376257⟩