title: Severe FOXP3+ and naïve T lymphopenia in a non-IPEX form of autoimmune enteropathy combined with an immunodeficiency.
abstract: OBJECTIVE
  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(+)CD4(+) 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(+) cells and other lymphocyte populations.
  
  
  METHODS
  We analyzed the major lymphocyte subsets and the FOXP3(+) 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(+)CD4(+) T cells, both in circulation and in the highly inflamed intestinal mucosa, but mutations in the FOXP3 locus were excluded. The blood FOXP3(+) pool was devoid of CD25(high) cells, but the few regulatory CD25(+) 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.
authors.affiliation: Unité du Développement des Lymphocytes, Institut Pasteur, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Zuber
authors.forename: Manuelle
authors.initials: M
authors.lastname: Viguier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lemaitre
authors.forename: Valérie
authors.initials: V
authors.lastname: Senée
authors.forename: Natacha
authors.initials: N
authors.lastname: Patey
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Elain
authors.forename: Frédéric
authors.initials: F
authors.lastname: Geissmann
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
authors.forename: Laurent
authors.initials: L
authors.lastname: Ferradini
authors.forename: Cécile
authors.initials: C
authors.lastname: Julier
authors.forename: Antonio
authors.initials: A
authors.lastname: Bandeira
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017074:Common Variable Immunodeficiency / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D007410:Intestinal Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008231:Lymphopenia / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D013577:Syndrome
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit