Coeliac Disease: What Can We Learn from Prospective Studies About Disease Risk?

Overview

Journal Lancet Child Adolesc Health

Specialty Pediatrics

Date 2023 Nov 16

PMID 37972632

Authors

Marisa Stahl

Sibylle Koletzko

Carin Andren Aronsson

Katri Lindfors

Edwin Liu

Daniel Agardh

Affiliations

Soon will be listed here.

Abstract

Paediatric prospective studies of coeliac disease with longitudinal collection of biological samples and clinical data offer a unique perspective on disease risk. This Review highlights the information now available from international paediatric prospective studies on genetic and environmental risk factors for coeliac disease. In addition, recent omics studies have made it possible to study complex interactions between genetic and environmental factors and thereby further our insight into the causes of the disease. In the future, paediatric prospective studies will be able to provide more detailed risk prediction models combining genes, the environment, and biological corroboration from multiomics. Such studies could also contribute to biomarker development and an improved understanding of disease pathogenesis.

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References

Husby S, Koletzko S, Korponay-Szabo I, Kurppa K, Mearin M, Ribes-Koninckx C . European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr. 2019; 70(1):141-156. DOI: 10.1097/MPG.0000000000002497. View

Leonard M, Valitutti F, Karathia H, Pujolassos M, Kenyon V, Fanelli B . Microbiome signatures of progression toward celiac disease onset in at-risk children in a longitudinal prospective cohort study. Proc Natl Acad Sci U S A. 2021; 118(29. PMC: 8307711. DOI: 10.1073/pnas.2020322118. View

Gutierrez-Achury J, Zhernakova A, Pulit S, Trynka G, Hunt K, Romanos J . Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease. Nat Genet. 2015; 47(6):577-8. PMC: 4449296. DOI: 10.1038/ng.3268. View

Kemppainen K, Lynch K, Liu E, Lonnrot M, Simell V, Briese T . Factors That Increase Risk of Celiac Disease Autoimmunity After a Gastrointestinal Infection in Early Life. Clin Gastroenterol Hepatol. 2016; 15(5):694-702.e5. PMC: 5576726. DOI: 10.1016/j.cgh.2016.10.033. View

Af Segerstad E, Liu X, Uusitalo U, Agardh D, Andren Aronsson C . Sources of dietary gluten in the first 2 years of life and associations with celiac disease autoimmunity and celiac disease in Swedish genetically predisposed children: The Environmental Determinants of Diabetes in the Young (TEDDY) study. Am J Clin Nutr. 2022; 116(2):394-403. PMC: 9348971. DOI: 10.1093/ajcn/nqac086. View

Tan I, Coutinho de Almeida R, Modderman R, Stachurska A, Dekens J, Barisani D . Circulating miRNAs as Potential Biomarkers for Celiac Disease Development. Front Immunol. 2021; 12:734763. PMC: 8688806. DOI: 10.3389/fimmu.2021.734763. View

Lindfors K, Lin J, Lee H, Hyoty H, Nykter M, Kurppa K . Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children: the TEDDY study. Gut. 2019; 69(8):1416-1422. PMC: 7234892. DOI: 10.1136/gutjnl-2019-319809. View

Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S . Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014; 371(14):1295-303. DOI: 10.1056/NEJMoa1400697. View

Vriezinga S, Auricchio R, Bravi E, Castillejo G, Chmielewska A, Crespo Escobar P . Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med. 2014; 371(14):1304-15. DOI: 10.1056/NEJMoa1404172. View

10.

Marild K, Dong F, Lund-Blix N, Seifert J, Baron A, Waugh K . Gluten Intake and Risk of Celiac Disease: Long-Term Follow-up of an At-Risk Birth Cohort. Am J Gastroenterol. 2019; 114(8):1307-1314. PMC: 6684402. DOI: 10.14309/ajg.0000000000000255. View

11.

Jansen M, van Zelm M, Groeneweg M, Jaddoe V, Dik W, Schreurs M . The identification of celiac disease in asymptomatic children: the Generation R Study. J Gastroenterol. 2017; 53(3):377-386. PMC: 5847176. DOI: 10.1007/s00535-017-1354-x. View

12.

Stordal K, Kahrs C, Tapia G, Agardh D, Kurppa K, Stene L . Review article: exposure to microbes and risk of coeliac disease. Aliment Pharmacol Ther. 2020; 53(1):43-62. DOI: 10.1111/apt.16161. View

13.

Romanos J, Rosen A, Kumar V, Trynka G, Franke L, Szperl A . Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants. Gut. 2013; 63(3):415-22. PMC: 3933173. DOI: 10.1136/gutjnl-2012-304110. View

14.

Canova C, Zabeo V, Pitter G, Romor P, Baldovin T, Zanotti R . Association of maternal education, early infections, and antibiotic use with celiac disease: a population-based birth cohort study in northeastern Italy. Am J Epidemiol. 2014; 180(1):76-85. DOI: 10.1093/aje/kwu101. View

15.

Tapia G, Chuda K, Kahrs C, Stene L, Kramna L, Marild K . Parechovirus Infection in Early Childhood and Association With Subsequent Celiac Disease. Am J Gastroenterol. 2021; 116(4):788-795. DOI: 10.14309/ajg.0000000000001003. View

16.

Marild K, Kahrs C, Tapia G, Stene L, Stordal K . Infections and risk of celiac disease in childhood: a prospective nationwide cohort study. Am J Gastroenterol. 2015; 110(10):1475-84. DOI: 10.1038/ajg.2015.287. View

17.

Bjorck S, Lynch K, Brundin C, Agardh D . Repeated Screening Can Be Restricted to At-Genetic-Risk Birth Cohorts. J Pediatr Gastroenterol Nutr. 2015; 62(2):271-5. DOI: 10.1097/MPG.0000000000000946. View

18.

Sen P, Carlsson C, Virtanen S, Simell S, Hyoty H, Ilonen J . Persistent Alterations in Plasma Lipid Profiles Before Introduction of Gluten in the Diet Associated With Progression to Celiac Disease. Clin Transl Gastroenterol. 2019; 10(5):1-10. PMC: 6602763. DOI: 10.14309/ctg.0000000000000044. View

19.

Stene L, Honeyman M, Hoffenberg E, Haas J, Sokol R, Emery L . Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol. 2006; 101(10):2333-40. DOI: 10.1111/j.1572-0241.2006.00741.x. View

20.

Sharma A, Liu X, Hadley D, Hagopian W, Liu E, Chen W . Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort. PLoS One. 2016; 11(3):e0152476. PMC: 4807782. DOI: 10.1371/journal.pone.0152476. View