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

Simple item page
dc.contributor.authorKansu Tanca, Aydan
dc.contributor.departmentTıp Fakültesitr_TR
dc.contributor.otherKuloğlu, Z
dc.date.accessioned2020-04-02T08:59:18Z
dc.date.available2020-04-02T08:59:18Z
dc.date.issued2014-06
dc.description.abstractBACKGROUND: 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.tr_TR
dc.identifier.endpage1659tr_TR
dc.identifier.issue6tr_TR
dc.identifier.startpage1651tr_TR
dc.identifier.urihttps://doi.org/10.1016/j.jaci.2014.02.034.tr_TR
dc.identifier.urihttp://hdl.handle.net/20.500.12575/70882
dc.identifier.volume133tr_TR
dc.language.isoentr_TR
dc.relation.isversionof10.1016/j.jaci.2014.02.034.tr_TR
dc.relation.journalJ Allergy Clin Immunol.tr_TR
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Başka Kurum Yazarıtr_TR
dc.subjectIL-21; common variable immunodeficiency; early-onset inflammatory bowel disease; exome sequencingtr_TR
dc.titleEarly-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency.tr_TR
dc.typeArticletr_TR

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
1-s2.0-S0091674914002991-main.pdf
Size:
2.59 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.62 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Makale