Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab

Pediatr Pulmonol. 2012 Jan;47(1):84-7. doi: 10.1002/ppul.21520. Epub 2011 Sep 7.


Autoimmune polyendocrine syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECD) is a disorder caused by mutations in the autoimmune regulator (AIRE) gene. In some APS-1 patients, significant pulmonary disease is observed. Autoantibodies directed against the potassium channel regulatory protein (KCNRG), found in epithelial cells of terminal bronchioles, have been suggested as a marker for pulmonary disease in APS-1 patients. We report two patients with APS-1; one with and one without lung disease. Patient 1 had multiple admissions for pneumonia and respiratory insufficiency, required non-invasive ventilation, and had findings of bronchiectasis on thoracic imaging and significant lymphocytic infiltrates of the airways on lung biopsy. To verify the autoimmune cause of pulmonary symptoms APS-1 patients, both were tested in a blinded manner for the presence of autoantibodies to KCNRG in serum. We found that only Patient 1 had autoantibodies present. Additionally, Patient 1 had progressive disease despite treatment with several immunomodulating agents, including corticosteroids, azathioprine, and mycophenolate. Patient 1 had a lung biopsy performed which was consistent with B cell lymphocytic aggregates. Rituximab treatment was initiated with apparent good response. This report illustrates the practical use of KCNRG autoantibodies to identify APS-1 patients with pulmonary risk and the successful use of the monoclonal antibody, Rituximab, to treat pulmonary disease in APS-1 patients.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Autoantibodies / analysis
  • Biomarkers / analysis
  • Child
  • Female
  • Humans
  • Immunologic Factors / therapeutic use
  • Lung Diseases / diagnosis
  • Lung Diseases / drug therapy
  • Male
  • Polyendocrinopathies, Autoimmune / diagnosis*
  • Polyendocrinopathies, Autoimmune / drug therapy
  • Potassium Channels / analysis
  • Potassium Channels / immunology*
  • Rituximab
  • Syndrome


  • Antibodies, Monoclonal, Murine-Derived
  • Autoantibodies
  • Biomarkers
  • Immunologic Factors
  • KCNRG protein, human
  • Potassium Channels
  • Rituximab

Supplementary concepts

  • Autoimmune polyendocrinopathy syndrome, type 1