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

被引：39

作者：

Fremond, Marie-Louise ^{[1
]}

Legendre, Marie ^{[2
,3
,4
]}

Fayon, Michael ^{[5
,6
]}

Clement, Annick ^{[2
,3
,7
]}

Filhol-Blin, Emilie ^{[2
,3
]}

Richard, Nicolas ^{[7
]}

Berdah, Laura ^{[7
]}

Roullaud, Sylvie ^{[8
]}

Rice, Gillian, I ^{[9
]}

Bondet, Vincent ^{[10
,11
]}

Duffy, Darragh ^{[10
,11
]}

Sileo, Chiara ^{[12
]}

le Pointe, Hubert Ducou ^{[12
]}

Begueret, Hugues ^{[13
]}

Coulomb, Aurore ^{[14
]}

Neven, Benedicte ^{[15
,16
]}

Amselem, Serge ^{[2
,3
]}

Crow, Yanick ^{[1
,17
]}

Nathan, Nadia ^{[2
,3
,7
]}

机构：

[1] Paris Descartes Univ, Imagine Inst, Lab Neurogenet & Neuroinflammat, Sorbonne Paris Cite, Paris, France

[2] INSERM, Inserm UMR S933, Paris, France

[3] Sorbonne Univ, Paris, France

[4] Sorbonne Univ, Trousseau Hosp, AP HP, Mol Genet Dept, Paris, France

[5] Bordeaux Univ Hosp, Cardiothorac Res Ctr U1045, Pediat Pulmonol, Bordeaux, France

[6] Bordeaux Univ Hosp, Cardiothorac Res Ctr U1045, CIC 1401, Bordeaux, France

[7] Sorbonne Univ, Trousseau Hosp, AP HP, Pediat Pulmonol & Reference Ctr Rare Lung Dis, F-75012 Paris, France

[8] CH Angouleme, Pediat Dept, Angouleme, Poitou Charente, France

[9] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Div Evolut & Genom Sci,Sch Biol Sci, Manchester, Lancs, England

[10] Inst Pasteur, Inserm 1223, Paris, France

[11] Inst Pasteur, Lab Dendrit Cell Immunobiol, Paris, France

[12] Sorbonne Univ, Trousseau Hosp, AP HP, Imaging Dept, Paris, France

[13] Haut Leveque Univ Hosp, Pathol Dept, Pessac, France

[14] Sorbonne Univ, Hop Trousseau, AP HP, Pathol Dept, Paris, France

[15] Paris Descartes Univ, Lab Immunogenet Pediat Autoimmun, Sorbonne Paris Cite, Inserm UMR 1163, Paris, France

[16] Necker Enfants Malad Hosp, AP HP, Paediat Hematol Immunol & Rheumatol Dept, Paris, France

[17] Univ Edinburgh, Ctr Genom & Expt Med, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland

来源：

THORAX | 2020年 / 75卷 / 01期

关键词：

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

D O I：

10.1136/thoraxjnl-2019-213892

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

COPA (coatomer subunit alpha) 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 IFN alpha (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.

引用

页码：92 / 95

页数：4

共 6 条

[1] Detection of interferon alpha protein reveals differential levels and cellular sources in disease [J].

Rodero, Mathieu P. ;

Decalf, Jeremie ;

Bondet, Vincent ;

Hunt, David ;

Rice, Gillian I. ;

Werneke, Scott ;

McGlasson, Sarah L. ;

Alyanakian, Marie-Alexandra ;

Bader-Meunier, Brigitte ;

Barnerias, Christine ;

Bellon, Nathalia ;

Belot, Alexandre ;

Bodemer, Christine ;

Briggs, Tracy A. ;

Desguerre, Isabelle ;

Fremond, Marie-Louise ;

Hully, Marie ;

van den Maagdenberg, Arn M. J. M. ;

Melki, Isabelle ;

Meyts, Isabelle ;

Musset, Lucile ;

Pelzer, Nadine ;

Quartier, Pierre ;

Terwindt, Gisela M. ;

Wardlaw, Joanna ;

Wiseman, Stewart ;

Rieux-Laucat, Frederic ;

Rose, Yoann ;

Neven, Benedicte ;

Hertel, Christina ;

Hayday, Adrian ;

Albert, Matthew L. ;

Rozenberg, Flore ;

Crow, Yanick J. ;

Duffy, Darragh .

JOURNAL OF EXPERIMENTAL MEDICINE, 2017, 214 (05) :1547-1555

[2] Lung Involvement in Children with Hereditary Autoinflammatory Disorders [J].

Tarantino, Giusyda ;

Esposito, Susanna ;

Andreozzi, Laura ;

Bracci, Benedetta ;

D'Errico, Francesca ;

Rigante, Donato .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (12)

[3] New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare® cohort [J].

Taytard, Jessica ;

Nathan, Nadia ;

de Blic, Jacques ;

Fayon, Mickael ;

Epaud, Ralph ;

Deschildre, Antoine ;

Troussier, Francoise ;

Lubrano, Marc ;

Chiron, Raphael ;

Reix, Philippe ;

Cros, Pierrick ;

Mahloul, Malika ;

Michon, Delphine ;

Clement, Annick ;

Corvol, Harriet .

ORPHANET JOURNAL OF RARE DISEASES, 2013, 8

[4] Analysis of pulmonary features and treatment approaches in the COPA syndrome [J].

Tsui, Jessica L. ;

Estrada, Oscar A. ;

Deng, Zimu ;

Wang, Kristin M. ;

Law, Christopher S. ;

Elicker, Brett M. ;

Jones, Kirk D. ;

Dell, Sharon D. ;

Gudmundsson, Gunnar ;

Hansdottir, Sif ;

Helfgott, Simon M. ;

Volpi, Stefano ;

Gattorno, Marco ;

Waterfield, Michael R. ;

Chan, Alice Y. ;

Chung, Sharon A. ;

Ley, Brett ;

Shum, Anthony K. .

ERJ OPEN RESEARCH, 2018, 4 (02)

[5] Type I interferon pathway activation in COPA syndrome [J].

Volpi, Stefano ;

Tsui, Jessica ;

Mariani, Marcello ;

Pastorino, Claudia ;

Caorsi, Roberta ;

Sacco, Oliviero ;

Ravelli, Angelo ;

Shum, Anthony K. ;

Gattorno, Marco ;

Picco, Paolo .

CLINICAL IMMUNOLOGY, 2018, 187 :33-36

[6] COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis [J].

Watkin, Levi B. ;

Jessen, Birthe ;

Wiszniewski, Wojciech ;

Vecel, Timothy J. ;

Jan, Max ;

Sha, Youbao ;

Thamsen, Maike ;

Santos-Cortez, Regie L. P. ;

Lee, Kwanghyuk ;

Gambint, Tomasz ;

Forbes, Lisa R. ;

Law, Christopher S. ;

Stray-Pedersenzt, Asbjorg ;

Cheng, Mickie H. ;

Mace, Emily M. ;

Anderson, Mark S. ;

Liu, Dongfang ;

Tang, Ling Fung ;

Nicholas, Sarah K. ;

Nahmod, Karen ;

Makedonas, George ;

Canter, Debra L. ;

Kwok, Pui-Yan ;

Hicks, John ;

Jones, Kirk D. ;

Penney, Samantha ;

Jhangiani, Shalini N. ;

Rosenblum, Michael D. ;

Dell, Sharon D. ;

Waterfield, Michael R. ;

Papa, Feroz R. ;

Muzny, Donna M. ;

Zaitlen, Noah ;

Leal, Suzanne M. ;

Gonzaga-Jaureguit, Claudia ;

Boerwinkle, Eric ;

Eissa, N. Tony ;

Gibbs, Richard A. ;

Lupski, James R. ;

Orange, Jordan S. ;

Shum, Anthony K. .

NATURE GENETICS, 2015, 47 (06) :654-660

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