title: Copa Syndrome: a Novel Autosomal Dominant Immune Dysregulatory Disease.
abstract: Inherently defective immunity typically results in either ineffective host defense, immune regulation, or both. As a category of primary immunodeficiency diseases, those that impair immune regulation can lead to autoimmunity and/or autoinflammation. In this review we focus on one of the most recently discovered primary immunodeficiencies that leads to immune dysregulation: "Copa syndrome". Copa syndrome is named for the gene mutated in the disease, which encodes the alpha subunit of the coatomer complex-I that, in aggregate, is devoted to transiting molecular cargo from the Golgi complex to the endoplasmic reticulum (ER). Copa syndrome is autosomal dominant with variable expressivity and results from mutations affecting a narrow amino acid stretch in the COPA gene-encoding COPα protein. Patients with these mutations typically develop arthritis and interstitial lung disease with pulmonary hemorrhage representing a striking feature. Immunologically Copa syndrome is associated with autoantibody development, increased Th17 cells and pro-inflammatory cytokine expression including IL-1β and IL-6. Insights have also been gained into the underlying mechanism of Copa syndrome, which include excessive ER stress owing to the impaired return of proteins from the Golgi, and presumably resulting aberrant cellular autophagy. As such it represents a novel cellular disorder of intracellular trafficking associated with a specific clinical presentation and phenotype.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vece
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Texas Children's Hospital Center for Human ImmunoBiology, Houston, TX.
authors.forename: Levi B
authors.initials: LB
authors.lastname: Watkin
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Texas Children's Hospital Center for Human ImmunoBiology, Houston, TX.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nicholas
authors.affiliation: Texas Children's Hospital Center for Human ImmunoBiology, Houston, TX.
authors.forename: Debra
authors.initials: D
authors.lastname: Canter
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Braun
authors.affiliation: Texas Children's Hospital, Houston, TX.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Guillerman
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX.
authors.forename: Karen W
authors.initials: KW
authors.lastname: Eldin
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Texas Children's Hospital Center for Human ImmunoBiology, Houston, TX.
authors.forename: Grant
authors.initials: G
authors.lastname: Bertolet
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Scott
authors.initials: S
authors.lastname: McKinley
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Texas Children's Hospital Center for Human ImmunoBiology, Houston, TX.
authors.forename: Marietta
authors.initials: M
authors.lastname: de Guzman
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Texas Children's Hospital Center for Human ImmunoBiology, Houston, TX.
authors.forename: Lisa
authors.initials: L
authors.lastname: Forbes
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Texas Children's Hospital Center for Human ImmunoBiology, Houston, TX.
authors.forename: Ivan
authors.initials: I
authors.lastname: Chinn
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.|Texas Children's Hospital Center for Human ImmunoBiology, Houston, TX.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
mesh_terms: D001168:Arthritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020756:Coatomer Protein / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008171:Lung Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D020756:Coatomer Protein
keywords: Autoimmunity; arthritis; autosomal dominant; interstitial lung disease; primary immunodeficiency