%0 Journal Article %T COPA syndrome, 5 years after: Where are we? %+ Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163) %+ CHU Trousseau [APHP] %+ Maladies génétiques d'expression pédiatrique (U933) %A Frémond, Marie-Louise %A Nathan, Nadia %Z We thank the Assistance Publique Hôpitaux de Paris, Sorbonne Université and Centre Université de Paris, Paris, France; the Institut National de la Santé et de la Recherche Médicale (Inserm); the Imagine Institute, Paris, France; the national networks for rare lung diseases: Centre de référence des maladies respiratoires rares (RespiRare), Centre de référence des maladies pulmonaires rares (OphaLung) and Filière de soins pour les maladies respira-toires rares (RespiFIL); the national networks for rare autoimmune and autoinflammatory diseases: Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant (RAISE) and Filière de soins des maladies auto-immunes et auto-inflammatoires rares (FAI2R); the Rare Disease Cohort (RaDiCo)-ILD project (ANR-10-COHO-0003); the FP7-305653-child-EU project; the COST Action European networkfor translational research in children’s and adult interstitial lung disease (COST-ILD) project (CA16125) and the Fondation Square. %< avec comité de lecture %@ 1297-319X %J Joint Bone Spine %I Elsevier Masson %V 88 %N 2 %P 105070 %8 2021-03 %D 2021 %R 10.1016/j.jbspin.2020.09.002 %M 32919065 %K Arthritis %K Autoinflammation %K COPA %K Diffuse alveolar haemorrhage %K Interferon %K Interstitial lung disease %Z Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tractJournal articles %X Heterozygous missense mutations in COPA, encoding coatomer protein subunit alpha (COPA), cause an interferonopathy mainly associating lung, joint and kidney involvement. This rare autoinflammatory disease is characterised by variable expression and a remarkably high frequency of clinical non-penetrance. Lung features, predominantly chronic diffuse alveolar haemorrhage (DAH), are observed in almost patients and can result in end-stage respiratory insufficiency. The initially described phenotype was broadened to include isolated DAH or lupus nephritis. Rare manifestations reminiscent of other monogenic interferonopathies occur. This indicates the need for careful clinical evaluation in patients with suspicion or diagnosis of COPA syndrome. Considering the dominant inheritance model and the highly variable phenotype, ranging from severe multi-organic disorder to non-penetrance, a careful family screening is recommended. New insights in disease pathogenesis have linked COPA mutations to STING-mediated interferon signalling. Beside a variable efficacy of 'classical' immunosuppressive drugs, Janus kinase (JAK) inhibitors constitute a promising treatment in COPA syndrome, and further targeted therapies are awaited. %G English %2 https://inserm.hal.science/inserm-04011131/document %2 https://inserm.hal.science/inserm-04011131/file/1-s2.0-S1297319X2030155X-main.pdf %L inserm-04011131 %U https://inserm.hal.science/inserm-04011131 %~ INSERM %~ APHP %~ U933 %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-MEDECINE %~ SU-MED %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SANTE %~ SU-TI %~ ANR %~ ALLIANCE-SU