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Record W4416109210 · doi:10.70962/jhi.20250009

IRF4 haploinsufficiency in a multiplex family with Whipple’s disease

2025· article· en· W4416109210 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueJournal of Human Immunity · 2025
Typearticle
Languageen
FieldMedicine
TopicWhipple's Disease and Interleukins
Canadian institutionsHospital for Sick Children
FundersNational Center for Research ResourcesNational Institute of Allergy and Infectious DiseasesNational Institutes of HealthStavros Niarchos FoundationCenter for Clinical and Translational Science, University of Illinois at ChicagoFondation pour la Recherche MédicaleInstitut National de la Santé et de la Recherche MédicaleNational Center for Advancing Translational SciencesAgence Nationale de la RechercheInserm TransfertFondation Maladies RaresRockefeller UniversityInstitut Necker-Enfants MaladesSt. Giles Foundation
KeywordsHaploinsufficiencyIRF4Missense mutationDiseaseTranscription factorGene

Abstract

fetched live from OpenAlex

Tropheryma whipplei is the bacterial agent responsible for Whipple’s disease (WD). However, WD occurs only very rarely in T. whipplei-infected individuals. We investigated the cause of disease in two relatives with WD. We studied a son and his mother, both presenting an articular form of WD, at the ages of 38 and 60 years, respectively, these episodes occurring five years apart. Both were otherwise healthy. We performed whole-exome sequencing, characterized a candidate variant biochemically, and performed an immunological analysis on the patients’ leukocytes. Both patients were heterozygous for a rare missense variant of the gene encoding the transcription factor IRF4 (p.R25S), for which haploinsufficiency was previously reported to underlie WD in a large multiplex family. This variant was hypomorphic for DNA binding and transcription induction. It did not exert negative dominance. Immunity was otherwise normal in these two patients. Haploinsufficiency for IRF4 can thus underlie WD in T. whipplei–infected individuals from at least two unrelated families.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.173
Threshold uncertainty score0.486

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.019
GPT teacher head0.309
Teacher spread0.290 · 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