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Record W4413221301 · doi:10.1101/2025.08.05.25332527

Human germline biallelic loss-of-function <i>OSMR</i> variants cause severe allergic disease

2025· preprint· en· W4413221301 on OpenAlexaff
Mehul Sharma, Simran Samra, Yihui Liu, Alyssa James, Christina Michalski, Pariya Yousefi, Kate L. Del Bel, Henry Y. Lu, Ashish Sharma, Maja Tarailo‐Graovac, Joshua Dalmann, Lily Buder, Bhavi P. Modi, Britt I. Drögemöller, Géraldine Blanchard‐Rohner, Christof Senger, Wingfield Rehmus, Julie Prendiville, Massimo Mangino, Colin J.D. Ross, Clara D.M. van Karnebeek, Wyeth W. Wasserman, Pascal M. Lavoie, P. M. Prathibha, Catherine M. Biggs, Michael Boehnke, Leena Kinnunen, Heikki A. Koistinen, Margaret L. McKinnon, Siddaramappa J. Patil, Diana K. Bayer, Jonathan J. Lyons, Stuart E. Turvey

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsUniversity of ManitobaChildren's Hospital Research Institute of ManitobaAlberta Children's HospitalBC Children's HospitalUniversity of British Columbia
Fundersnot available
KeywordsSTAT5BiologyPhenotypeProbandSignal transductionImmunologyReceptorLoss functionGermlineCancer researchGeneticsMutationGene

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.029
GPT teacher head0.304
Teacher spread0.275 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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Same venuemedRxiv→Same topicAsthma and respiratory diseases→French-language works237,207→