Potential celiac children: 9-year follow-up on a gluten-containing diet.
OBJECTIVE
Potential celiac disease (CD) is defined by the presence of serum anti-tissue-transglutaminase (anti-TG2) antibodies and normal duodenal mucosa. The major clinical problem is the management of asymptomatic patients and how to predict the development of villous atrophy. This prospective longitudinal cohort study describes the natural history of potential CD up to 9 years and explores risk factors associated with the development of mucosal damage.


METHODS
Two hundred and ten potential CD children were eligible for the study; 175/210 asymptomatic children were left on a gluten-containing diet. Antibodies and clinical symptoms were checked every 6 months, and a small bowel biopsy was taken every 2 years to evaluate histological, immunohistochemical, and anti-TG2 deposits. Patients were genotyped for HLA and a set of non-HLA CD-associated genes.


RESULTS
Forty-three percent of patients showed persistently elevated anti-TG2 level, 20% became negative during follow-up, and 37% showed a fluctuant anti-TG2 course with transiently negative values. At 3 years of follow-up, 86% of cases remained potential; 73 and 67% still had normal duodenal architecture at 6 and 9 years, respectively. Male sex, slight mucosal inflammation at time 0, and a peculiar genetic profile delineate a cohort of individuals who were prone to develop mucosal damage during time.


CONCLUSIONS
A sizeable proportion of asymptomatic potential celiac patients showed fluctuation or negativization of antibody production, and many of these, with persistently positive anti-TG2, did not develop mucosal damage after 9 years of follow-up. Celiac population is a multivariate aggregate of individuals with different genetic and phenotypic profiles. Caution is required before prescribing a gluten-free diet for life to asymptomatic individuals with potential CD.
Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
Renata
R
Auricchio
Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
Antonella
A
Tosco
Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
Emanuela
E
Piccolo
Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
Martina
M
Galatola
Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
Valentina
V
Izzo
Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
Mariantonia
M
Maglio
Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
Francesco
F
Paparo
Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
Riccardo
R
Troncone
Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.
Luigi
L
Greco
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D001706:Biopsy; D002446:Celiac Disease / Q000178:diet therapy* / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D019204:GTP-Binding Proteins; D005838:Genotype; D005983:Glutens / Q000008:administration & dosage*; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007150:Immunohistochemistry; D007223:Infant; D007413:Intestinal Mucosa; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012307:Risk Factors; D011503:Transglutaminases / Q000276:immunology*
D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D007070:Immunoglobulin A; D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins