Decreased circulating iNKT cell numbers in refractory coeliac disease.
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.
Bernardo
David
D
Mucosal Immunology Lab, Department of Paediatrics and Immunology-IBGM, University of Valladolid, Valladolid, Spain.
van Hoogstraten
Ingrid M W
IM
Verbeek
Wieke H M
WH
Peña
A Salvador
AS
Mearin
M Luisa
ML
Arranz
Eduardo
E
Garrote
José Antonio
JA
Scheper
Rik J
RJ
Schreurs
Marco W J
MW
Bontkes
Hetty J
HJ
Mulder
Chris J J
CJ
von Blomberg
B Mary E
BM
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*
D005983:Glutens