Abstract
The COPA syndrome is a monogenic, autoimmune lung and joint disorder first identified in 2015. This study sought to define the main pulmonary features of the COPA syndrome in an international cohort of patients, analyse patient responses to treatment and highlight when genetic testing should be considered.
We established a cohort of subjects (N=14) with COPA syndrome seen at multiple centres including the University of California, San Francisco, CA, USA. All subjects had one of the previously established mutations in the COPA gene, and had clinically apparent lung disease and arthritis. We analysed cohort characteristics using descriptive statistics.
All subjects manifested symptoms before the age of 12 years, had a family history of disease, and developed diffuse parenchymal lung disease and arthritis. 50% had diffuse alveolar haemorrhage. The most common pulmonary findings included cysts on chest computed tomography and evidence of follicular bronchiolitis on lung biopsy. All subjects were positive for anti-neutrophil cytoplasmic antibody, anti-nuclear antibody or both and 71% of subjects had rheumatoid factor positivity. All subjects received immunosuppressive therapy.
COPA syndrome is an autoimmune disorder defined by diffuse parenchymal lung disease and arthritis. We analysed an international cohort of subjects with genetically confirmed COPA syndrome and found that common pulmonary features included cysts, follicular bronchiolitis and diffuse alveolar haemorrhage. Common extrapulmonary features included early age of onset, family history of disease, autoantibody positivity and arthritis. Longitudinal data demonstrated improvement on chest radiology but an overall decline in pulmonary function despite chronic treatment.
Abstract
When to consider COPA syndrome, a Mendelian disorder with lung disease and arthritis, plus a review of treatments used http://ow.ly/hWv130k21vT
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Author contributions: J.L. Tsui analysed the data and wrote the manuscript. O.A. Estrada recruited subjects and gathered clinical data. Z. Deng, K.M. Wang and C.S. Law analysed the data and wrote the manuscript. B.M. Elicker provided radiology services including analysis. K.D. Jones provided pathology services including analysis. S.D. Dell, G. Gudmundsson, S. Hansdottir, S.M. Helfgott, S. Volpi, M. Gattorino, A.Y. Chan and M.R. Waterfield provided clinical care and analysed clinical data. B. Ley and S.A. Chung analysed the data and wrote the manuscript. A.K. Shum supervised the study and wrote the manuscript.
Conflict of interest: None declared
Support statement: A.K. Shum is supported by NIH grants R01HL122533 and R01AI137249, J.L. Tsui is supported by NIH grant F32HL131234, G. Gudmundsson is supported by a project grant from the Icelandic Research Fund (141513-051) and from the Landspitali Scientific Fund (A-2015-030 and A-2016-023), M.R. Waterfield is supported by NIH K08 AI121513-03, S. Volpi is supported by grant Telethon GGP15241A, and A.Y. Chan is supported by the Rheumatology Research Foundation Investigator Award. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received February 1, 2018.
- Accepted April 27, 2018.
- Copyright ©ERS 2018
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.