IRF4 haploinsufficiency in a multiplex family with Whipple’s disease
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".