Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of KCNRG as a Bronchial Autoantigen

Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4396-401. doi: 10.1073/pnas.0809986106. Epub 2009 Feb 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Obstruction
  • Autoantibodies / analysis
  • Autoantigens / immunology*
  • Autoimmunity / immunology*
  • Bronchi / immunology*
  • Bronchioles / immunology
  • Bronchioles / pathology
  • Cause of Death
  • Epithelial Cells / immunology
  • Gene Library
  • Humans
  • Immunoprecipitation
  • Lung Diseases / etiology
  • Lung Diseases / immunology*
  • Polyendocrinopathies, Autoimmune / complications*
  • Polyendocrinopathies, Autoimmune / immunology*
  • Potassium Channels / analysis
  • Potassium Channels / genetics
  • Potassium Channels / immunology*
  • Pulmonary Disease, Chronic Obstructive / immunology
  • RNA, Messenger / analysis
  • Recombinant Proteins / immunology

Substances

  • Autoantibodies
  • Autoantigens
  • KCNRG protein, human
  • Potassium Channels
  • RNA, Messenger
  • Recombinant Proteins