Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Journal of Allergy and Clinical Immunology Année : 2014

Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency

E. Salzer
  • Fonction : Auteur
A. Kansu
  • Fonction : Auteur
H. Sic
  • Fonction : Auteur
P. Majek
  • Fonction : Auteur
A. Ikinciogullari
  • Fonction : Auteur
F. E. Dogu
  • Fonction : Auteur
N. K. Prengemann
  • Fonction : Auteur
E. Santos-Valente
  • Fonction : Auteur
W. F. Pickl
  • Fonction : Auteur
I. Bilic
  • Fonction : Auteur
S. A. Ban
  • Fonction : Auteur
Z. Kuloglu
  • Fonction : Auteur
A. M. Demir
  • Fonction : Auteur
A. Ensari
  • Fonction : Auteur
M. Rizzi
  • Fonction : Auteur
H. Eibel
  • Fonction : Auteur
K. Boztug
  • Fonction : Auteur

Résumé

BACKGROUND: Alterations of immune homeostasis in the gut can result in development of inflammatory bowel disease (IBD). Recently, Mendelian forms of IBD have been discovered, as exemplified by deficiency of IL-10 or its receptor subunits. In addition, other types of primary immunodeficiency disorders might be associated with intestinal inflammation as one of their leading clinical presentations. OBJECTIVE: We investigated a large consanguineous family with 3 children who presented with early-onset IBD within the first year of life, leading to death in infancy in 2 of them. METHODS: Homozygosity mapping combined with exome sequencing was performed to identify the molecular cause of the disorder. Functional experiments were performed to assess the effect of IL-21 on the immune system. RESULTS: A homozygous mutation in IL21 was discovered that showed perfect segregation with the disease. Deficiency of IL-21 resulted in reduced numbers of circulating CD19(+) B cells, including IgM(+) naive and class-switched IgG memory B cells, with a concomitant increase in transitional B-cell numbers. In vitro assays demonstrated that mutant IL-21(Leu49Pro) did not induce signal transducer and activator of transcription 3 phosphorylation and immunoglobulin class-switch recombination. CONCLUSION: Our study uncovers IL-21 deficiency as a novel cause of early-onset IBD in human subjects accompanied by defects in B-cell development similar to those found in patients with common variable immunodeficiency. IBD might mask an underlying primary immunodeficiency, as illustrated here with IL-21 deficiency.
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Dates et versions

hal-02168078 , version 1 (28-06-2019)

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Citer

E. Salzer, A. Kansu, H. Sic, P. Majek, A. Ikinciogullari, et al.. Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency. Journal of Allergy and Clinical Immunology, 2014, 133, pp.1651--9 e12. ⟨10.1016/j.jaci.2014.02.034⟩. ⟨hal-02168078⟩
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