Type I interferon pathway activation in COPA syndrome

Volpi, Stefano; Tsui, Jessica; Mariani, Marcello; Pastorino, Claudia; Caorsi, Roberta; Sacco, Oliviero; Ravelli, Angelo; Shum, Anthony K.; Gattorno, Marco; Picco, Paolo

doi:10.1016/j.clim.2017.10.001

Cited by 111 publications

(97 citation statements)

References 12 publications

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“…All COPA mutations previously identified in the literature map to exons eight and nine in the highly conserved WD40 functional domain of the COPA protein [2,8,13,14,17,18]. e p.Gly853Asp variant identified in this report is instead found in the C-terminal domain of the protein which could account for the attenuated phenotype in these individuals compared to phenotypes from WD40-domain mutations.…”

Section: Discussionmentioning

confidence: 67%

Behçet Disease-Like Symptoms with a Novel COPA Mutation

Anderson¹,

Hatch

Cardinal

et al. 2020

Case Reports in Genetics

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COPA syndrome is a recently described autosomal dominant disorder with key immune dysregulation caused by defects within the COPA gene. These mutations lead to endoplasmic reticulum stress and autoimmune response with upregulation of Th17 cytokines. The clinical phenotype of COPA syndrome primarily comprised pulmonary disease, arthritis, and renal disease secondary to immune dysregulation, with onset of symptoms commonly in the first decade of life. Herein, we describe a family with an attenuated Behçet-like phenotype of COPA syndrome, further expanding the phenotypic understanding of this syndrome.

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Section: Discussionmentioning

confidence: 67%

Behçet Disease-Like Symptoms with a Novel COPA Mutation

Anderson¹,

Hatch

Cardinal

et al. 2020

Case Reports in Genetics

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“…72 Similarly to patients carriers of TMEM173 gene mutations, COPA mutations induce a strong upregulation of interferon-stimulated genes. 73 Most of the patients (76%) were under 5 years, 95% had joint pain, and all had ILD or alveolar hemorrhage. 72 Screening for autoantibodies showed positivity for ANCA (71%), antinuclear antibodies (67%), and rheumatoid factor (43%).…”

Section: Heritable Forms Of Pulmonary Fibrosis Associated With Ancamentioning

confidence: 96%

“…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. 74 Lung biopsies of older patients show NSIP and follicular bronchiolitis or diffuse interstitial pulmonary neuroendocrine cell hyperplasia.…”

Section: Heritable Forms Of Pulmonary Fibrosis Associated With Ancamentioning

confidence: 99%

Antineutrophil Cytoplasmic Antibody–Associated Lung Fibrosis

Borie

Crestani

2018

Semin Respir Crit Care Med

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Pulmonary fibrosis is observed in a substantial number of patients with ANCA-associated vasculitis (AAV), 15% in a recent German series, and may be more frequent in Asian populations. ANCA are usually of anti-MPO specificity and microscopic polyangiitis is the most frequent vasculitis. Pulmonary fibrosis may increase the risk of death in patients with AAV. Treatment for AAV in patients with lung fibrosis should follow the international guidelines for vasculitis. The role of anti-fibrotic drugs (pirfenidone, nintedanib) in this condition is still unknown. Pulmonary fibrosis precedes the diagnosis of AAV or is diagnosed concomitantly in most of the cases. Interestingly, 4% to 35% of patients with pulmonary fibrosis are ANCA-positive, but only 7% to 23% of the patients with pulmonary fibrosis and anti-MPO will develop AAV during follow-up. ANCA positivity may be detected in idiopathic or non idiopathic pulmonary fibrosis. In the absence of vasculitis, the detection of ANCA does not influence the diagnostic work-up of patients with lung fibrosis. If an Idiopathic Pulmonary Fibrosis diagnosis is considered, an anti-fibrotic therapy should be considered, according to local and international guidelines.

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“…The first report of COPA syndrome in 2015 described variants in the COPA gene as a cause of autoimmune-mediated lung disease in 5 multigenerational families (5); subsequent studies have demonstrated an increased number of individuals diagnosed as having COPA syndrome. The COPα protein is involved in cellular trafficking, and mutated COPα proteins appear to increase endoplasmic reticulum stress (5), which is a potential trigger for enhanced interferon signaling (6) and the generation of inflammatory T cells (5).…”

mentioning

confidence: 99%