Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen

Medientyp: E-Artikel

Titel: Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen

Beteiligte: Alimohammadi, Mohammad; Dubois, Noémie; Sköldberg, Filip; Hallgren, Åsa; Tardivel, Isabelle; Hedstrand, Håkan; Haavik, Jan; Husebye, Eystein S.; Gustafsson, Jan; Rorsman, Fredrik; Meloni, Antonella; Janson, Christer; Vialettes, Bernard; Kajosaari, Merja; Egner, William; Sargur, Ravishankar; Pontén, Fredrik; Amoura, Zahir; Grimfeld, Alain; De Luca, Filippo; Betterle, Corrado; Perheentupa, Jaakko; Kämpe, Olle; Carel, Jean-Claude

Erschienen: Proceedings of the National Academy of Sciences, 2009

Sprache: Englisch

DOI: 10.1073/pnas.0809986106

ISSN: 0027-8424; 1091-6490

Schlagwörter: Multidisciplinary

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Beschreibung: Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

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