Respiratory Infections and the Risk of Celiac Disease.

BACKGROUND AND OBJECTIVES: The increasing incidence of celiac disease (CD) suggests that common infections before the onset of autoimmune diseases could be an important factor in switching the immune response. We aimed to explore the relationship between early clinical events and the development of CD in genetically predisposed infants. METHODS: In this study, 373 newborns from families with at least 1 relative with CD were recruited, and human leukocyte antigen DQ2- or DQ8-positive infants were followed up with clinical and serological evaluations. Cross tabulation and odds ratios were used to explore the risk associated with single variables, and logistic regression analysis was performed to determine the variables that contributed to the risk of developing CD. Stepwise discriminant analysis was used to determine which variables could distinguish case patients from controls before diagnosis. RESULTS: The cumulative incidence of CD in this cohort was 6% at 3 years and 13.5% at 5 years of age, and l34 children (14%) developed CD before the sixth year of life. An analysis of adverse events showed a higher frequency of respiratory tract infections among CD patients during the first 24 months of life. In a stepwise discriminant analysis, which included sex and human leukocyte antigen risk class, only respiratory infections in the second and first years of life significantly contributed to discrimination of case patients versus controls. CONCLUSIONS: A multivariate model of discriminant analysis showed that the frequency of respiratory infections in the first 2 years of life could distinguish children who developed CD from those who did not.

Introduction of gluten, HLA status, and the risk of celiac disease in children.

BACKGROUND: The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear. METHODS: We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS: Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS: Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.).

Celiac disease: predictors of compliance with a gluten-free diet in adolescents and young adults.

AIMS: To identify risk as well as protective factors related to compliance with the gluten-free diet in a cohort of teenagers with celiac disease (CD). PATIENTS AND METHODS: Two hundred four patients with CD (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria) older than or equal to 13 years and residents of Campania (southern Italy) were enrolled in the study. Patients underwent clinical examination and blood sampling, and were interviewed about school performance, social relationships, family integration, smoking habit, and compliance with a gluten-free diet. Anti-tissue transglutaminase antibodies were assayed with an enzyme-linked immunosorbent assay. RESULTS: One hundred fifty of 204 (73.5%) reported no dietary transgressions, and 54 of 204 (26.5%) reported occasional or frequent transgressions. During the previous month 29 of 54 (53.7%) poor compliers ate from 0.001 to 1 g of gluten per day, 14 (25.9%) from 1 to 5 g, and 11 (20.4%) more than 5 g. The daily intake of gluten was significantly related to anti-tissue transglutaminase antibodies (chi2 = 38.872, P = 0.000). Height was below the third percentile in 19 of 204 (9.3%), and weight was above the 97th percentile in 20 of 204 (9.8%). Diet compliance did not seem to influence the weight and height. One hundred eleven of 150 good compliers (74%) and 31 of 54 (57.4%) poor compliers were asymptomatic. Most patients reported good family relationships (88.7%), social relationships (91.2%), and school integration (88.2%). Alternatively, 54% of patients reported some limitation in their social life. Compliance was good in patients who reported excellent school integration (83%) and social relationships (81%). CONCLUSION: Optimal school integration significantly contributes to the likelihood of good compliance. A better understanding within the school environment about CD-related issues could improve motivation to adhere to a gluten-free diet.

HLA related genetic risk for coeliac disease.

BACKGROUND: Several studies have shown an elevated prevalence of coeliac disease (CD) in sibs of coeliac patients (risk 8-12%). AIM AND METHOD: We evaluated the risk that sibs of children with CD will also develop CD. This cohort of 188 Italian families was composed of probands with CD, at least one sib and both parents. CD status was determined and human leucocyte antigen (HLA)-DQ genotyping performed in all family members. The study also used a dataset of Italian triads (127 probands and both their parents) also genotyped for HLA-DQ. RESULTS: The overall risk that a sib of a CD patient will develop the disease was estimated at 10% in this sample. The risk estimate ranged from 0.1% to 29% when HLA-DQ information of the proband, parents and sib was considered. We found a negligible risk (lower than 1%) for 40% of the sibs of probands, a risk greater than 1% but less than 10% for 30%, and finally a high or very high risk (above 25%) in one-third of families. CONCLUSION: These results make it possible to provide more accurate information to parents with a child with CD about the real risk for another child. An antenatal estimate of the order of risk of CD is now possible. Specific follow-up can thus be offered for babies at high risk.