{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:51:13Z","timestamp":1787010673506,"version":"build-2736575974"},"posted":{"date-parts":[[2025,8,8]]},"group-title":"Allergy and Immunology","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  OSMR\u03b2 (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\n                  <jats:italic>OSMR<\/jats:italic>\n                  , which encodes OSMR\u03b2. Patients had a unifying phenotype for severe widespread, early-onset atopic dermatitis, peripheral eosinophilia, and elevated serum IgE. Patient OSMR\u03b2 variants were not appropriately expressed on the cell surface compared to OSMR\u03b2\n                  <jats:sup>WT<\/jats:sup>\n                  . Patient\n                  <jats:italic>OSMR<\/jats:italic>\n                  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-\n                  <jats:italic>OSMR<\/jats:italic>\n                  . Together, these data establish that human germline biallelic loss-of-function\n                  <jats:italic>OSMR<\/jats:italic>\n                  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.\n                <\/jats:p>","DOI":"10.1101\/2025.08.05.25332527","type":"posted-content","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T01:35:12Z","timestamp":1754703312000},"source":"Crossref","is-referenced-by-count":1,"title":["Human germline biallelic loss-of-function\n                  <i>OSMR<\/i>\n                  variants cause severe allergic disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9591-0415","authenticated-orcid":false,"given":"Mehul","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-3139","authenticated-orcid":false,"given":"Simran","family":"Samra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9726-6611","authenticated-orcid":false,"given":"Alyssa","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9093-5325","authenticated-orcid":false,"given":"Christina","family":"Michalski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6306-6204","authenticated-orcid":false,"given":"Pariya","family":"Yousefi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7669-9530","authenticated-orcid":false,"given":"Kate 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