Gliadin-reactive T cells in Italian children from preventCD cohort at high risk of celiac disease.
Newborns at high risk of celiac disease (CD) were recruited in Italy in the context of the PreventCD study and closely monitored for CD, from 4 months up to a mean age of 8 years at follow-up. The aim of our study was to investigate intestinal T-cell reactivity to gliadin at the first clinical and/or serological signs of CD.



Gliadin-reactive T-cell lines were generated from intestinal biopsies of 19 HLA-DQ2-or HLA-DQ8-positive children. At biopsy, 11 children had a diagnosis of acute CD, two of potential CD, and six were non-celiac controls. Immune reactivity was evaluated against gliadin and known immunogenic peptides from α-, γ-, or ω-gliadins. The role of deamidation by transglutaminase (tTG) in determining the immunogenicity of gliadin was also investigated.



Most of the children with CD (either acute or potential) had an inflammatory response to gliadin. Notably, signs of T-cell reactivity to gliadin were also found in some non-celiac subjects, in which IFN-γ responses occurred mainly when regulatory IL-10 and TGF-β cytokines were blocked. Interestingly, PreventCD children reacted to gliadin peptides found active in adult CD patients, and tTG deamidation markedly enhanced gliadin recognition.



T cells reactive to gliadin can be detected in the intestine of children at high risk of developing CD, in some cases also in the presence of a normal mucosa and negative CD-associated antibodies. Furthermore, children at a very early stage of CD recognize the same gliadin epitopes that are active in adult CD patients. Tissue transglutaminase strongly enhances gluten T-cell immunogenicity in early CD.
Institute of Food Sciences, National Research Council, Avellino, Italy.
Alessandra
A
Camarca
Department of Medical and Translational Sciences, Section of Pediatrics and European Laboratory for the Food Induced Diseases (E.L.F.I.D), University of Naples Federico II, Naples, Italy.
Renata
R
Auricchio
Institute of Protein Biochemistry, National Research Council, Naples, Italy.
Stefania
0000-0003-1080-9391
S
Picascia
Institute of Food Sciences, National Research Council, Avellino, Italy.
Olga
O
Fierro
Department of Medical and Translational Sciences, Section of Pediatrics and European Laboratory for the Food Induced Diseases (E.L.F.I.D), University of Naples Federico II, Naples, Italy.
Mariantonia
M
Maglio
Department of Medical and Translational Sciences, Section of Pediatrics and European Laboratory for the Food Induced Diseases (E.L.F.I.D), University of Naples Federico II, Naples, Italy.
Erasmo
E
Miele
Department of Pediatrics, University Hospital of Salerno, Salerno, Italy.
Basilio
B
Malamisura
Department of Medical and Translational Sciences, Section of Pediatrics and European Laboratory for the Food Induced Diseases (E.L.F.I.D), University of Naples Federico II, Naples, Italy.
Luigi
L
Greco
Department of Medical and Translational Sciences, Section of Pediatrics and European Laboratory for the Food Induced Diseases (E.L.F.I.D), University of Naples Federico II, Naples, Italy.
Riccardo
R
Troncone
Department of Medical and Translational Sciences, Section of Pediatrics and European Laboratory for the Food Induced Diseases (E.L.F.I.D), University of Naples Federico II, Naples, Italy.|Institute of Protein Biochemistry, National Research Council, Naples, Italy.
Carmen
C
Gianfrani
D000941:Antigens / Q000276:immunology; D002446:Celiac Disease / Q000276:immunology*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007223:Infant; D007558:Italy; D008213:Lymphocyte Activation; D008297:Male; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D005903:Gliadin
antigluten T-cell lines; celiac disease; children at genetic risk; early gut immune response