Human germline biallelic loss-of-function OSMR variants cause severe allergic disease
Year: 2026
Type: article
Abstract: ABSTRACT OSMRβ (Oncostatin M receptor beta), a member of the IL-6 superfamily of cell surface receptors, binds OSM and IL-31 and plays a critical role in human immunity. We identified probands from four kindreds with biallelic damaging variants in OSMR , which encodes OSMRβ. Patients had a unifying phenotype for severe widespread, early-onset atopic dermatitis, peripheral eosinophilia, and elevated serum IgE. Patient OSMRβ variants were not appropriately expressed on the cell surface compared to OSMRβ WT . Patient OSMR variants showed significantly reduced OSM-mediated activation of STAT1, STAT3, and STAT5 and distinct transcriptional changes in primary dermal fibroblasts, including loss of interferon and inflammatory signatures. These defects were rescued upon lentiviral transduction of WT- OSMR . Together, these data establish that human germline biallelic loss-of-function OSMR variants cause severe allergic disease. We anticipate that this discovery will facilitate the recognition of additional affected individuals and the full definition of this novel primary atopic disorder.
Source: Journal of Human Immunity
Authors: Simran Samra, Mehul Sharma, Julia Körholz, Yihui Liu, Alyssa James, Christina Michalski, Pariya Yousefi, Kate L. Del Bel, Henry Y. Lu, Ashish A. Sharma, Maja Tarailo-Graovac, Joshua Dalmann, Lily Buder, Bhavi Modi, Ralf Wiedemuth, Liam Golding, Britt Drögemöller, Géraldine Blanchard-Rohner, Christof Senger, Wingfield Rehmus, Julie S. Prendiville, Massimo Mangino, Colin J. Ross, Clara D.M. van Karnebeek, Wyeth W. Wasserman, Sergio D. Rosenzweig, Julie Niemela, Pascal M. Lavoie, P. M. Prathibha, Oliver Wegehaupt, Catherine M. Biggs, Michael Boehnke, Leena Kinnunen, Heikki A. Koistinen, Margaret L. McKinnon, Jonas Maximillian Breuer, Jana Schönenkorb, Robert Brock, Sarah Thull, Christian Netzer, Clara Velmans, Norah Altuwaijri, Issam R. Hamadah, Ruqaiah Altassan, Ahmed Alfares, Sateesh Maddirevula, Siddaramappa Jagdish Patil, Diana K. Bayer, Jonathan J. Lyons, Stuart E. Turvey
Institutions: University of British Columbia, BC Children's Hospital, University Hospital Carl Gustav Carus, Technische Universität Dresden, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Emory University, University of Calgary, Alberta Children's Hospital Research Institute, Children's Hospital Research Institute of Manitoba, University of Manitoba, University of Geneva, University Hospital of Geneva, Amsterdam University Medical Centers, University of Amsterdam, BC Children's Hospital Research Institute, National Institutes of Health Clinical Center, Narayana Health, Mazumdar Shaw Medical Centre, University of Freiburg, University Medical Center Freiburg, University of Michigan, University of Helsinki, Finnish Institute for Health and Welfare, Helsinki University Hospital, Minerva Foundation, University of Cologne, University Hospital Cologne, King Faisal Specialist Hospital & Research Centre, University of Iowa Stead Family Children’s Hospital, University of California San Diego, VA San Diego Healthcare System
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funders: U.S. Department of Health and Human Services, Children's Hospital Foundation, BC Children’s Hospital Foundation, BC Children's Hospital, Broad Institute, Genome British Columbia, Albert-Ludwigs-Universität Freiburg, University of British Columbia, European Society for Immunodeficiencies, National Institutes of Health, Canadian Institutes of Health Research, Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Intramural Research Program
OpenAlex ID: W7162694581