title: Decreased circulating iNKT cell numbers in refractory coeliac disease.
abstract: BACKGROUND
  A small proportion of coeliac disease (CD) patients become refractory (RCD) to a gluten-free diet (GFD) showing uncontrolled immune-mediated enteropathy. Some of these patients exhibit a high risk to develop enteropathy-associated T-cell lymphoma (EATL).
  
  
  OBJECTIVE
  The aim of the study was to find whether a lack of circulating homeostatic T cells, such as Treg, Tgammadelta(+) or iNKT cells would be associated with the development of RCD or EATL.
  
  
  METHODS
  We investigated in a total of 137 CD patients [28 untreated, 80 responsive to GFD and 29 RCD (14 type I and 15 type II)] and 73 age-matched healthy volunteers the frequency of Treg, Tgammadelta(+) and iNKT lymphocytes by flow cytometric analysis of peripheral blood.
  
  
  RESULTS
  Circulating Tgammadelta(+) cell and Treg frequencies in RCD were comparable to those in healthy controls. However, RCD patients had significantly reduced numbers of circulating iNKT cells, as compared to age-matched patients responding to a GFD. This reduction was similar in RCD patients with and without aberrant intraepithelial lymphocytes and in patients with EATL. Circulating iNKT cell numbers were not reduced in untreated coeliac patients. GFD treated patients had a significantly increased proportion of CD4(+) iNKT cells.
  
  
  CONCLUSIONS
  Follow-up studies are necessary to determine whether CD4(+) iNKT cells control the immune response against gluten and their absence contributes to the progression to RCD and EATL.
authors.affiliation: Mucosal Immunology Lab, Department of Paediatrics and Immunology-IBGM, University of Valladolid, Valladolid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Bernardo
authors.forename: Ingrid M W
authors.initials: IM
authors.lastname: van Hoogstraten
authors.forename: Wieke H M
authors.initials: WH
authors.lastname: Verbeek
authors.forename: A Salvador
authors.initials: AS
authors.lastname: Peña
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Mearin
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arranz
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Garrote
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Marco W J
authors.initials: MW
authors.lastname: Schreurs
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: Bontkes
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002446:Celiac Disease / Q000276:immunology* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004032:Diet; D005260:Female; D005983:Glutens / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D005983:Glutens