1. Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of KCNRG as a Bronchial Autoantigen
- Author
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Alimohammadi, Mohammad, Dubois, Noemie, Sköldberg, Filip, Hallgren, Åsa, Tradivel, Isabelle, Hedstrand, Håkan, Haavik, Jan, Husebye, Eystein, Gustafsson, Jan, Rorsman, Fredrik, Meloni, Antonella, Janson, Christer, Vilattes, Bernard, Kajosaari, Merja, Egner, William, Sargur, Ravishankar, Amoura, Zahir, Grimfeld, Alain, Pontén, Fredrik, De Luca, Filippo, Betterle, Corrado, Perheentupa, Jaakko, Kämpe, Olle, Alimohammadi, Mohammad, Dubois, Noemie, Sköldberg, Filip, Hallgren, Åsa, Tradivel, Isabelle, Hedstrand, Håkan, Haavik, Jan, Husebye, Eystein, Gustafsson, Jan, Rorsman, Fredrik, Meloni, Antonella, Janson, Christer, Vilattes, Bernard, Kajosaari, Merja, Egner, William, Sargur, Ravishankar, Amoura, Zahir, Grimfeld, Alain, Pontén, Fredrik, De Luca, Filippo, Betterle, Corrado, Perheentupa, Jaakko, and Kämpe, Olle
- Abstract
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.
- Published
- 2009
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