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

Marie-Louise Fremond; Marie Legendre; Michael Fayon; Annick Clement; Emilie Filhol-Blin; Nicolas Richard; Laura Berdah; Sylvie Roullaud; Gillian, I Rice; Vincent Bondet; Darragh Duffy; Chiara Sileo; Hubert Ducou le Pointe; Hugues Begueret; Aurore Coulomb; Benedicte Neven; Serge Amselem; Yanick Crow; Nadia Nathan

doi:10.1136/thoraxjnl-2019-213892

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

Marie-Louise Fremond, Marie Legendre, Michael Fayon, Annick Clement, Emilie Filhol-Blin, Nicolas Richard, Laura Berdah, Sylvie Roullaud, Gillian, I Rice, Vincent Bondet, Darragh Duffy, Chiara Sileo, Hubert Ducou le Pointe, Hugues Begueret, Aurore Coulomb, Benedicte Neven, Serge Amselem, Yanick Crow, Nadia Nathan

Division of Evolution, Infection and Genomics

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Abstract

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.

Original language	English
Pages (from-to)	92-95
Journal	Thorax
Volume	75
Issue number	1
Early online date	13 Dec 2019
DOIs	https://doi.org/10.1136/thoraxjnl-2019-213892
Publication status	Published - 1 Jan 2020

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/thoraxjnl-2019-213892

2019 COPA_revision_unmarked_VFAccepted author manuscript, 52.7 KB

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Fremond, M.-L., Legendre, M., Fayon, M., Clement, A., Filhol-Blin, E., Richard, N., Berdah, L., Roullaud, S., Rice, G. I., Bondet, V., Duffy, D., Sileo, C., le Pointe, H. D., Begueret, H., Coulomb, A., Neven, B., Amselem, S., Crow, Y., & Nathan, N. (2020). Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage. Thorax, 75(1), 92-95. https://doi.org/10.1136/thoraxjnl-2019-213892

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abstract = "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 = "paediatric interstitial lung disease, rare lung diseases, systemic disease and lungs, massive haemoptysis, paediatric lung disaese",

author = "Marie-Louise Fremond and Marie Legendre and Michael Fayon and Annick Clement and Emilie Filhol-Blin and Nicolas Richard and Laura Berdah and Sylvie Roullaud and Rice, {Gillian, I} and Vincent Bondet and Darragh Duffy and Chiara Sileo and {le Pointe}, {Hubert Ducou} and Hugues Begueret and Aurore Coulomb and Benedicte Neven and Serge Amselem and Yanick Crow and Nadia Nathan",

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Fremond, M-L, Legendre, M, Fayon, M, Clement, A, Filhol-Blin, E, Richard, N, Berdah, L, Roullaud, S, Rice, GI, Bondet, V, Duffy, D, Sileo, C, le Pointe, HD, Begueret, H, Coulomb, A, Neven, B, Amselem, S, Crow, Y & Nathan, N 2020, 'Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage', Thorax, vol. 75, no. 1, pp. 92-95. https://doi.org/10.1136/thoraxjnl-2019-213892

TY - JOUR

T1 - Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage

AU - Fremond, Marie-Louise

AU - Legendre, Marie

AU - Fayon, Michael

AU - Clement, Annick

AU - Filhol-Blin, Emilie

AU - Richard, Nicolas

AU - Berdah, Laura

AU - Roullaud, Sylvie

AU - Rice, Gillian, I

AU - Bondet, Vincent

AU - Duffy, Darragh

AU - Sileo, Chiara

AU - le Pointe, Hubert Ducou

AU - Begueret, Hugues

AU - Coulomb, Aurore

AU - Neven, Benedicte

AU - Amselem, Serge

AU - Crow, Yanick

AU - Nathan, Nadia

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

KW - paediatric interstitial lung disease

KW - rare lung diseases

KW - systemic disease and lungs

KW - massive haemoptysis

KW - paediatric lung disaese

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DO - 10.1136/thoraxjnl-2019-213892

M3 - Article

SN - 0040-6376

VL - 75

SP - 92

EP - 95

JO - Thorax

JF - Thorax

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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