Prevalence of Celiac Disease in a Long-Term Study of a Spanish At-Genetic-Risk Cohort from the General Population

Objectives: To perform long-term celiac disease (CD) screening in an HLA-DQ2 (+) cohort from the general population and to assess the influence of risk genotypes on its development. Methods: In 2004, an HLA-DQ2 (+) cohort was selected. After the first CD screening at age 2–3 years, we performed a follow-up screening 8–10 years later. Anti-TG2 antibodies were determined using a rapid test kit. Results were confirmed by serum IgA anti-TG2 and IgA EMA determination. CD diagnosis was carried out by intestinal biopsies. Four HLA-DQ2 genotypic groups were used: G1: DQ2.5/DQ2.5 (G1A) or DQ2.5/ DQ2.2 (G1B); G2: DQ2.2/DQ7.5 (DQ2.5 trans); G3: DQ2.5/ X; G4: DQ2.2/X. Results: CD prevalence after 10 years of follow-up was 5.8% (95%CI 3.8–8.7). One of every three HLA-DQ2(+) children carried at least one haplotype DQ2.2 or DQ7. The homozygous genotype DQ2.5/DQ2.5 and the HLA-DQ2.5 trans genotype increased CD risk 4- and 3-fold, respectively. The homozygous genotype DQ2.5/ DQ2.2 did not increase the CD risk. Children carrying G1 or G2 genotypes were diagnosed with CD earlier and more frequently during the follow-up compare with those carrying G3 or G4 genotypes. 81% of children with spontaneous antibody negativization after the first screening maintained negative antibodies. Conclusions: A repeated screening of at-risk children during their follow-up allowed us to diagnose new CD cases. In our cohort, HLA- DQ2.5 trans genotype conferred a higher risk in the development of CD than HLA- DQ2.5/DQ2.2. The majority of children with potential CD and CD autoimmunity at 10 years of age remained healthy. Address correspondence and reprint requests to Sonia Fernández-Fernández, PhD, Pediatric Gastroenterology Unit, Department of Pediatrics, Hospital Universitario Severo Ochoa. Avenida Orellana s/n 28911 Leganés, Madrid, Spain (e-mail: soniaferfer@hotmail.com). Received 31 July, 2018 Accepted 17 October, 2018 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). The authors report no conflicts of interest. The study was funded by the UAX-Santander Foundation through two grants obtained in 2015 and 2016. The funding source did not play any role in the study's design, data collection, analyses, nor in the interpretation of data, writing, or submission of this article. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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