دورية أكاديمية
Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency
| العنوان: | Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency |
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| المؤلفون: | Salzer, E., Kansu, A., Sic, H., Majek, P., Ikinciogullari, A., Dogu, F. E., Prengemann, N. K., Santos-Valente, E., Pickl, W. F., Bilic, I., Ban, S. A., Kuloglu, Z., Demir, A. M., Ensari, A., Colinge, Jacques, Rizzi, M., Eibel, H., Boztug, K. |
| المساهمون: | Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| المصدر: | ISSN: 0091-6749 ; Journal of Allergy and Clinical Immunology ; https://hal.umontpellier.fr/hal-02168078Test ; Journal of Allergy and Clinical Immunology, 2014, 133, pp.1651--9 e12. ⟨10.1016/j.jaci.2014.02.034⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2014 |
| المجموعة: | Université de Montpellier: HAL |
| مصطلحات موضوعية: | Humans, Female, Male, Mutation, Signal Transduction, Models, Molecular, Amino Acid Sequence, Molecular Sequence Data, Child, Infant, Age of Onset, Preschool, Immunophenotyping, B-Lymphocyte Subsets/immunology/metabolism, Common Variable Immunodeficiency/*genetics/immunology/metabolism, Consanguinity, DNA Mutational Analysis, Immunoglobulin Class Switching, Immunoglobulin Isotypes/blood/immunology, Inflammatory Bowel Diseases/*genetics/immunology/metabolism, Interleukins/chemistry/*deficiency/*genetics, Lymphocyte Activation, Pedigree, Protein Conformation, Receptors, Interleukin-21/metabolism, Sequence Alignment, [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/24746753; hal-02168078; https://hal.umontpellier.fr/hal-02168078Test; PUBMED: 24746753 |
| DOI: | 10.1016/j.jaci.2014.02.034 |
| الإتاحة: | https://doi.org/10.1016/j.jaci.2014.02.034Test https://hal.umontpellier.fr/hal-02168078Test |
| رقم الانضمام: | edsbas.1B31AAF9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jaci.2014.02.034 |
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