Familial
Celiac Disease
Celiac disease arises in people with predisposing genetic factors, involving both HLA and non-HLA genetic variants.1,2
Due to these predisposing genetic factors, celiac disease can be hereditary. The risk of developing the condition depends on how closely related someone is to a person with celiac disease:1
In a retrospective cohort study of 104 patients with celiac disease and their first-degree relatives in the US:3
| Of 360 first-degree relatives screened, 44% were diagnosed with celiac disease |
Of 148 first-degree relatives diagnosed with celiac disease: |
| 6% had classic symptoms | |
| 66% had non-classic symptoms | |
| 28% were asymptomatic |
More than 90% of people with celiac disease will have one of either HLA-DQ2 or HLA-DQ8 haplotypes. Up to 40% of the general population carry these DQ types but only ~3% of the population has celiac disease, suggesting that there are other factors that work with the haplotypes to cause the condition.4
Genetic HLA testing
- In people with celiac disease, the most prevalent HLA haplotype combinations, in order of prevalence, are DQ2.5/DQ2.5, DQ2.5/DQ2.2 and DQ2.5/DQ2.85
- A negative HLA test can be useful in ruling out celiac disease, as the chance of developing celiac disease without an HLA haplotype is rare5
Guidelines: Tissue transglutaminase IgA autoantibodies (IgA tTg) and DQ testing in relatives of people with celiac disease
ESPGHAN
The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommends considering testing for celiac disease in children and adolescents who have first-degree relatives with celiac disease.8
ESsCD
The European Society for the Study of Celiac Disease (ESsCD) recommends HLA typing in both first- and second-degree relatives.2
- HLA typing can be considered as the first-line test for first-degree relatives
- Further workup is not needed in people who are negative for HLA-DQ2 or HLA-DQ8
- Members of families who have more than one individual with celiac disease are at higher risk of developing the condition and recommendations for screening should extend to all other family members, including second-degree relatives
ACG
The American College of Gastroenterology recommends testing for celiac disease in first-degree relatives.9
- Patients with a first-degree relative who has a confirmed diagnosis of celiac disease should be tested whether they are symptomatic or show laboratory evidence for celiac disease
- Testing should be considered in asymptomatic first-degree relatives of people with confirmed celiac disease
- Murch S, Jenkins H et al. Joint BSPGHAN and Coeliac UK guidelines for the diagnosis and management of coeliac disease in children. Arch Dis Child 2013;98:806-811
- Al-Toma A, Volta U et al. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J 2019;7:583-613
- Nellikkal S S, Hafed Y et al. High prevalence of celiac disease among screened first-degree relatives. Mayo Clin Proc 2019;94:1807-1813
- Sallese M, Lopetuso L R et al. Beyond the HLA genes in gluten-related disorders. Front Nutr 2020;7:575844
- Almeida L M, Gandolfi L et al. Presence of DQ2.2 associated with DQ2.5 increases the risk for celiac disease. Autoimmune Dis 2016;2016:5409653
- National Institute for Health and Care Excellence (NICE). NICE guideline 20. Coeliac disease: recognition, assessment and management, September 2015. Available at: https://www.nice.org.uk/guidance/ng20/resources/coeliac-disease-recognition-assessment-and-management-pdf-1837325178565. Accessed January 2025
- Ludvigsson J F, Bai J C et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014;63:1210-1228
- European Society for Paediatric Gastroenterology, Heptology and Nutrition (ESPGHAN). 2022 ESPGHAN position paper on follow-up and management of coeliac disease. Available at: https://www.espghan.org/knowledge-center/publications/Gastroenterology/ESPGHAN-Position-Paper-on-Follow-up-of-Coeliac-Disease-. Accessed January 2025
- Rubio-Tapia A, Hill I D et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol 2023;118:59-76
© NICE 2015 Coeliac disease: recognition, assessment and management. Available from www.nice.org.uk/guidance/ng20. All rights reserved. Subject to Notice of rights.
NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/ publication.