Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen.
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.
Alimohammadi
Mohammad
M
Department of Medical Sciences, University Hospital, Uppsala University, 751 85 Uppsala, Sweden. mohammad.alimohammadi@medsci.uu.se
Dubois
Noémie
N
Sköldberg
Filip
F
Hallgren
Asa
A
Tardivel
Isabelle
I
Hedstrand
Håkan
H
Haavik
Jan
J
Husebye
Eystein S
ES
Gustafsson
Jan
J
Rorsman
Fredrik
F
Meloni
Antonella
A
Janson
Christer
C
Vialettes
Bernard
B
Kajosaari
Merja
M
Egner
William
W
Sargur
Ravishankar
R
Pontén
Fredrik
F
Amoura
Zahir
Z
Grimfeld
Alain
A
De Luca
Filippo
F
Betterle
Corrado
C
Perheentupa
Jaakko
J
Kämpe
Olle
O
Carel
Jean-Claude
JC
D000402:Airway Obstruction; D001323:Autoantibodies / Q000032:analysis; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001980:Bronchi / Q000276:immunology*; D055745:Bronchioles / Q000276:immunology / Q000473:pathology; D002423:Cause of Death; D004847:Epithelial Cells / Q000276:immunology; D015723:Gene Library; D006801:Humans; D047468:Immunoprecipitation; D008171:Lung Diseases / Q000209:etiology / Q000276:immunology*; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications* / Q000276:immunology*; D015221:Potassium Channels / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; C473317:KCNRG protein, human; D015221:Potassium Channels; D012333:RNA, Messenger; D011994:Recombinant Proteins