Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen.Report as inadecuate




Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Medical Sciences 2 Immunologie, génétique et traitement des maladies métaboliques et du diabète 3 Département de nutrition, maldies métaboliques et endocrinologie 4 Department of Biomedicine 5 Division of Endocrinology 6 Department of Medicine 7 Department of Biosciences and Nutrition, Karolinska Institut 8 Pediatric Division II 9 The Hospital for Children and Adolescents 10 Clinical Immunology and Allergy Unit 11 Department of Genetics and Pathology, the Rudbeck Laboratory 12 Service de médecine interne CHU Pitié-Salpétrière 13 Unité Asthme et allergologie 14 Department of Pediatrics 15 Department of Medical and Surgical Sciences 16 Diabète de l-enfant et développement 17 Service d-endocrinologie

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.





Author: Mohammad Alimohammadi - Noémie Dubois - Filip Sköldberg - Asa Hallgren - Isabelle Tardivel - Håkan Hedstrand - Jan Haavik - Ey

Source: https://hal.archives-ouvertes.fr/



DOWNLOAD PDF




Related documents