Analysis of pulmonary features and treatment approaches in the COPA syndrome

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.

Genetic Disorders Should Be Considered Prior to Diagnosing Interstitial Pneumonia With Autoimmune Features: Comment on the Review by Wilfong et al

“…Radiographic findings can be consistent with nonspecific interstitial pneumonia, and histology can demonstrate interstitial lymphocytic infiltrates with germinal centers (5). These are patterns similar to ones in other autoimmune diseases and IPAF (7). Polyarthritis and kidney disease (often glomerulonephritis) are other predominant features of this disorder.…”

Behçet Disease-Like Symptoms with a Novel COPA Mutation

“…It is not yet fully clear whether increased 17 is causative to, or caused by, COPA inflammatory symptomatology. Whilst various immunosuppressive regimes have been effective in some shortterm improvement or stability particularly of the pulmonary symptoms of COPA syndrome, these may be limited in their long-term effectiveness [7]. 17 and related interleukins such as IL-17A have a significant role in gastrointestinal disorders such as 2…”

“…COPA syndrome has only recently been identified, initially in five families with various COPA mutations [2]. It is an autoimmune disease with early onset, usually by five years of age [2], and generally with a greater female-to-male ratio [2,7]. It is inherited in an autosomal dominant pattern, with variable penetrance and expressivity that can also reflect gender bias [8].…”

Antineutrophil Cytoplasmic Antibody–Associated Lung Fibrosis

“…The number of cyst then increases as the ground-glass opacities decrease, with a pattern suggestive of NSIP or lymphocytic interstitial pneumonia. 74 Cysts are commonly observed on CT. 75 Recently, two other patients were reported, one with a CT pattern suggestive of NSIP and the other with a CT showing cysts and tree-in-bud opacities. 73,76 Histopathological evaluation shows initially alveolar hemorrhage and pulmonary capillaritis with necrosis of the capillary walls, and neutrophils along the capillaries, but also lymphoid aggregates around airways.…”