title: Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab.
abstract: 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.
authors: Georgia Pediatric Pulmonology Associates, Atlanta, Georgia 3042, USA. JPopler@gppa.net
authors: Jonathan
authors: J
authors: Popler
authors: Mohammad
authors: M
authors: Alimohammadi
authors: Olle
authors: O
authors: Kämpe
authors: Frida
authors: F
authors: Dalin
authors: Megan K
authors: MK
authors: Dishop
authors: Jennifer M
authors: JM
authors: Barker
authors: Margaret
authors: M
authors: Moriarty-Kelsey
authors: Jennifer B
authors: JB
authors: Soep
authors: Robin R
authors: RR
authors: Deterding
mesh_terms: D000293:Adolescent; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001323:Autoantibodies / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D002648:Child; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008171:Lung Diseases / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis* / Q000188:drug therapy; D015221:Potassium Channels / Q000032:analysis / Q000276:immunology*; D000069283:Rituximab; D013577:Syndrome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D015415:Biomarkers; D007155:Immunologic Factors; C473317:KCNRG protein, human; D015221:Potassium Channels; D000069283:Rituximab