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Severe FOXP3+ and Naïve T Lymphopenia in a Non-IPEX Form of Autoimmune Enteropathy Combined With an Immunodeficiency.

Authors :
Zuber, Julien
Viguier, Manuelle
Lemaitre, Fabrice
Senée, Valérie
Patey, Natacha
Elain, Gaëlle
Geissmann, Frédéric
Fakhouri, Fadi
Ferradini, Laurent
Julier, Cécile
Bandeira, Antonio
Source :
Gastroenterology (00165085); May2007, Vol. 132 Issue 5, p1694-1704, 11p
Publication Year :
2007

Abstract

Background & Aims: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is the best-characterized form of a rare entity called autoimmune enteropathy (AIE). IPEX syndrome is due to mutations in the FOXP3 gene, a transcription factor essential for the development and function of the natural regulatory CD25<superscript>+</superscript>CD4<superscript>+</superscript> T cells. We studied a female patient with a polyautoimmune AIE syndrome resembling a mild form of IPEX syndrome but associated with recurrent bacterial infections and mild hypogammaglobulinemia. We hypothesized that this syndrome combined a deficit of FOXP3<superscript>+</superscript> cells and other lymphocyte populations. Methods: We analyzed the major lymphocyte subsets and the FOXP3<superscript>+</superscript> regulatory system in blood samples obtained during the 2-year period that followed the last autoimmune manifestation. Results: The patient had severe naïve T lymphopenia and a major deficit of FOXP3 <superscript>+</superscript>CD4<superscript>+</superscript> T cells, both in circulation and in the highly inflamed intestinal mucosa, but mutations in the FOXP3 locus were excluded. The blood FOXP3<superscript>+</superscript> pool was devoid of CD25<superscript>high</superscript> cells, but the few regulatory CD25<superscript>+</superscript> cells were functional. Intrinsic defects in the expression of CD25, FOXP3, and interleukin 2 were excluded. Upon activation, a small subset of cells, presumably committed to regulatory function, sustained expression of CD25 and FOXP3. Conclusions: Peripheral T lymphopenia of both naïve and natural regulatory T cells might be the consequence of defective thymic production or the short life span of exported T cells. This case sheds new light in the etiology of autoimmune manifestations in T-cell immunodeficiencies and in the heterogeneity of AIE. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
00165085
Volume :
132
Issue :
5
Database :
Supplemental Index
Journal :
Gastroenterology (00165085)
Publication Type :
Academic Journal
Accession number :
24963292
Full Text :
https://doi.org/10.1053/j.gastro.2007.02.034