Higher constitutive IL15Ra expression and lower IL-15 response threshold in Coeliac Disease patients

BERNARDO ORDIZ, D; GARROTE, JA; ALLEGRETTI, Y; LEON, A; GOMEZ, E; BERMEJO-MARTIN, J; CALVO, C; RIESTRA, S; FERNANDEZ-SALAZAR, L; BLANCO-QUIROS, A; CHIRDO, FG; ARRANZ, E

CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Oxford, UK

Lugar: Oxford Blackwell Scientific Publications; Año: 2008 vol. 154 p. 64 - 73

0009-9104

The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific.We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15Ra mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15Ra mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0·0334, on GCD P = 0·0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15Ra expression was only triggered in non-CD controls (P = 0·0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFNg (P = 0·0313, P = 0·0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine.