Article Dans Une Revue Journal of Human Immunity Année : 2026

IRF4 haploinsufficiency in a multiplex family with Whipple’s disease

Sinem Ünal
Stéphanie Dublanc
Hailun Li
Jean-Philippe Vernhes
Camille Soudée
Nabil Bel Feki
  • Fonction : Auteur
Martin Blondel
  • Fonction : Auteur
Aurélie Jourdes
  • Fonction : Auteur
Paul Legendre
  • Fonction : Auteur
Guillaume Le Guenno
  • Fonction : Auteur
Tom Le Voyer
  • Fonction : Auteur
Guillaume Lefevre
  • Fonction : Auteur
Jonathan London
  • Fonction : Auteur
Antoine Neel
  • Fonction : Auteur
Sébastien Ottaviani
Roderau Outh
  • Fonction : Auteur
Ailsa Robbins
  • Fonction : Auteur
Amélie Servettaz
  • Fonction : Auteur
Marc Scherlinger
  • Fonction : Auteur
Nicolas Schleinitz
Thibault Sixt
  • Fonction : Auteur
Vivien Béziat
Guillaume Vogt
Xavier Puéchal
Jean-Laurent Casanova
Jacinta Bustamante
Jérémie Rosain

Résumé

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.

Dates et versions

hal-05535919 , version 1 (04-03-2026)

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Citer

Sinem Ünal, Stéphanie Dublanc, Hailun Li, Jean-Philippe Vernhes, Vincent Meynier, et al.. IRF4 haploinsufficiency in a multiplex family with Whipple’s disease. Journal of Human Immunity, 2026, 2 (1), ⟨10.70962/jhi.20250009⟩. ⟨hal-05535919⟩
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