| Added by | mollevi |
|---|---|
| Last modified by | jacques.colinge |
| Group name | EquipeJC |
| Item Type | Journal Article |
| Title | Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency |
| Creator | Salzer et al. |
| Author | E. Salzer |
| Author | A. Kansu |
| Author | H. Sic |
| Author | P. Majek |
| Author | A. Ikinciogullari |
| Author | F. E. Dogu |
| Author | N. K. Prengemann |
| Author | E. Santos-Valente |
| Author | W. F. Pickl |
| Author | I. Bilic |
| Author | S. A. Ban |
| Author | Z. Kuloglu |
| Author | A. M. Demir |
| Author | A. Ensari |
| Author | J. Colinge |
| Author | M. Rizzi |
| Author | H. Eibel |
| Author | K. Boztug |
| Abstract | 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. |
| Publication | J Allergy Clin Immunol |
| Volume | 133 |
| Pages | 1651-9 e12 |
| Date | Jun 2014 |
| Journal Abbr | The Journal of allergy and clinical immunology |
| DOI | 10.1016/j.jaci.2014.02.034 |
| ISSN | 1097-6825 (Electronic) 0091-6749 (Linking) |
| Tags | Age of Onset, Amino Acid Sequence, B-Lymphocyte Subsets/immunology/metabolism, Child, Child, Preschool, Common Variable Immunodeficiency/*genetics/immunology/metabolism, Consanguinity, DNA Mutational Analysis, Female, Humans, Immunoglobulin Class Switching, Immunoglobulin Isotypes/blood/immunology, Immunophenotyping, Infant, Inflammatory Bowel Diseases/*genetics/immunology/metabolism, Interleukins/chemistry/*deficiency/*genetics, Lymphocyte Activation, Male, Models, Molecular, Molecular Sequence Data, Mutation, original, Pedigree, Protein Conformation, Receptors, Interleukin-21/metabolism, Sequence Alignment, Signal Transduction |
| Date Added | 2018/11/14 - 11:48:35 |
| Date Modified | 2019/05/14 - 20:58:23 |
| Notes and Attachments | (Note) (Note) 24746753 (Attachment) |
Institut de Recherche en Cancérologie de
