Current concepts in the pathogenesis of celiac disease
REVIEWS
Abstract
Introduction. Celiac disease is a chronic genetically determined immune-mediated disorder that develops in response to dietary gluten and is characterized by damage to the small intestinal mucosa with subsequent malabsorption syndrome and a wide spectrum of extraintestinal manifestations. The disease may manifest at any age and often remains undiagnosed due to the polymorphism of clinical symptoms and its similarity to other gastrointestinal disorders. The main etiological factor is gluten intake, the elimination of which leads to clinical and morphological remission. The aim — to analyze current concepts of the etiology, pathogenesis, diagnosis, and перспектив es of treatment of celiac disease. Materials and methods. A review of contemporary scientific publications was conducted, along with an analysis of histological specimens of the duodenal mucosa obtained from children with suspected celiac disease. Morphological assessment was performed according to the Marsh–Oberhuber classification using standard staining techniques. Results. Celiac disease was shown to result from the interaction between genetic predisposition (HLA-DQ2/DQ8) and immune mechanisms triggered by gluten. Diagnosis is based on a comprehensive evaluation of clinical manifestations, medical history, serological markers, and morphological changes in the small intestinal mucosa. Morphological alterations range from inflammatory infiltration to total villous atrophy. The disease is systemic in nature and is associated with involvement of the skin, kidneys, nervous, skeletal, and reproductive systems. Extraintestinal manifestations are mainly caused by the production of autoantibodies to tissue transglutaminase. In addition to a strict gluten-free diet, pathogenetic therapeutic approaches aimed at gluten modification, immune response modulation, and tolerance induction are currently under development. Conclusion. Celiac disease is a multisystem autoimmune disorder that requires a comprehensive diagnostic approach. A deeper understanding of its pathogenesis expands the possibilities for targeted therapy and prevention of complications.
References
1. Бельмер С.В., Ревнова М.О. Клинические проявления целиакии: на пути к ранней диагностике. Экспериментальная и клиническая гастроэнтерология. 2021;4(188):106–115. https://doi.org/10.31146/1682-8658-ecg-188-4-106-115.
2. Цукуров А.А., Цукурова Д.Д., Перепелица В.К., Чуб А.С., Сулейманов С.С., Фетисова Е.С. и др. Глютеновая энтеропатия: клинический случай. Международный научно-исследовательский журнал. 2024;11(149). EDN: OTTHZM. https://doi.org/10.60797/IRJ.2024.149.99.
3. Рославцева Е.А., Дмитриева Ю.А., Захарова И.Н., Боровик Т.Э., Потапов А.С., Сурков А.Н. и др. Целиакия у детей: проект клинических рекомендаций. Экспериментальная и клиническая гастроэнтерология. 2021;(4):199–227. https://doi.org/10.31146/1682-8658-ecg-188-4-199-227.
4. Аверкина Н.А., Баранов А.А., Бельмер С.В., Бораева Т.Т., Боровик Т.Э., Бушуева Т.В. и др. Целиакия-2025: проект клинических рекомендаций по диагностике и лечению целиакии у детей. Педиатрическая фармакология. 2025;22(4):495–522. https://doi.org/10.15690/pf.v22i4.2941.
5. Stanciu D., Staykov H., Dragomanova S., Tancheva L., Pop R.S., Ielciu I. et al. Gluten Unraveled: Latest Insights on Terminology, Diagnosis, Pathophysiology, Dietary Strategies, and Intestinal Microbiota Modulations — A Decade in Review. Nutrients. 2024;16(21):3636. https://doi.org/10.3390/nu16213636.
6. Дмитриева Ю.А., Рославцева Е.А., Курьянинова В.А., Захарова И.Н., Боровик Т.Э., Касаткина Е.Н. и др. Структура HLA-DR-DQ-генотипа у детей с целиакией. Медицинский совет. 2020;(10):74–80. EDN: SDLYER. https://doi.org/10.21518/2079-701X-2020-10-74-80.
7. Хавкин А.И., Налетов А.В., Куропятник П.И. Роль вирусов в патогенезе целиакии: современное состояние вопроса. Педиатрическая фармакология. 2024;21(4):369–374. https://doi.org/10.15690/pf.v21i4.2771.
8. Özakıncı H., Kırmızı A., Tural M., Kiremitçi S., Savaş B., Kuloğlu Z. et al. Duodenal bulb biopsy in the diagnostic work-up of coeliac disease. Virchows Arch. 2020;477(4):507–515. https://doi.org/10.1007/s00428-020-02832-6.
9. Doyle J.B., Lebwohl B. Celiac disease and nonceliac enteropathies. Curr Opin Gastroenterol. 2024;40(6):464–469. https://doi.org/10.1097/MOG.0000000000001048.
10. Størdal K., Kurppa K. Celiac disease, non-celiac wheat sensitivity, wheat allergy — clinical and diagnostic aspects. Semin Immunol. 2025;77:101930. https://doi.org/10.1016/j.smim.2025.101930.
11. Wieser H., Ciacci C., Soldaini C., Gizzi C., Pellegrini L., Santonicola A. Fertility in Celiac Disease: The Impact of Gluten on Male and Female Reproductive Health. Nutrients. 2025;17(9):1575. https://doi.org/10.3390/nu17091575.
12. Nurmi R., Korponay-Szabó I., Laurila K., Huhtala H., Niemelä O., Mustonen J. et al. Celiac Disease-Type Tissue Transglutaminase Autoantibody Deposits in Kidney Biopsies of Patients with Ig A Nephropathy. Nutrients. 2021;13(5):1594. https://doi.org/10.3390/nu13051594.
13. Rauhavirta T., Hietikko M., Salmi T., Lindfors K. Transglutaminase 2 and Transglutaminase 2 Autoantibodies in Celiac Disease: a Review. Clin Rev Allergy Immunol. 2019;57(1):23–38. https://doi.org/10.1007/s12016-016-8557-4.
14. Jafari E., Soleymani N., Hamidi M., Rahi A., Rezaei A., Azizian R. Celiac Disease: A Review from Genetic to Treatment. Iran Biomed J. 2024;28(1):8–14. https://doi.org/10.61186/ibj.4028.
15. Losurdo G., Di Leo M., Santamato E., Arena M., Rendina M., Luigiano C. et al. Serologic diagnosis of celiac disease: May it be suitable for adults? World J Gastroenterol. 2021;27(42):7233–7239. https://doi.org/10.3748/wjg.v27.i42.7233.
16. Iversen R., Sollid L.M. The Immunobiology and Pathogenesis of Celiac Disease. Annu Rev Pathol. 2023;18:47–70. https://doi.org/10.1146/annurev-pathmechdis-031521-032634.
17. Tamai T., Ihara K. Celiac Disease Genetics, Pathogenesis, and Standard Therapy for Japanese Patients. Int J Mol Sci. 2023;24(3):2075. https://doi.org/10.3390/ijms24032075.
18. Шаповалова Н.С., Новикова В.П., Ревнова М.О. и др. Гастроинтестинальные факторы риска развития анемии у детей с целиакией. Педиатр. 2019;10(5):5–12.
19. Laurikka P., Kivelä L., Kurppa K., Kaukinen K. Review article: Systemic consequences of coeliac disease. Aliment Pharmacol Ther. 2022;56(Suppl 1):S64–S72. https://doi.org/10.1111/apt.16912.
20. Kaunisto H., Salmi T., Lindfors K., Kemppainen E. Antibody Responses to Transglutaminase 3 in Dermatitis Herpetiformis: Lessons from Celiac Disease. Int J Mol Sci. 2022;23(6):2910. https://doi.org/10.3390/ijms23062910.
21. Ge Y.M., Peng S.L., Wang Q., Yuan J. Causality between Celiac disease and kidney disease: A Mendelian Randomization Study. Medicine (Baltimore). 2024;103(35):e39465. https://doi.org/10.1097/MD.0000000000039465.
22. Zambrano S., Parma B., Morabito V., Borini S., Romaniello R., Molteni M. et al. Celiac disease in autism spectrum disorder: data from an Italian child cohort. Ital J Pediatr. 2023;49(1):79. https://doi.org/10.1186/s13052-023-01484-x.
23. Kılıçoğlu M.S., Sayılır S., Yurdakul O.V., Aydin T., Koçhan K., Basaranoglu M. et al. Association between celiac disease and fibromyalgia and their severity: a cross-sectional study. Peer J. 2024;12:e17949. https://doi.org/10.7717/peerj.17949.
24. Новикова В.П., Шаповалова Н.С., Ревнова М.О. и др. Желудок как орган-мишень целиакии. Педиатр. 2018;9(4):64–72.
25. Lupu V.V., Sasaran M.O., Jechel E., Starcea I.M., Ioniuc I., Mocanu A. et al. Celiac disease — a pluripathological model in pediatric practice. Front Immunol. 2024;15:1390755. https://doi.org/10.3389/fimmu.2024.1390755.
26. Pop D., Ichim E.G., Farcău D. Nutritional Status in Children with Celiac Disease and Type 1 Diabetes Mellitus — A Narrative Review. Nutrients. 2025;17(4):728. https://doi.org/10.3390/nu17040728.
27. Discepolo V., Kelly C.P., Koning F., Schuppan D. How Future Pharmacologic Therapies for Celiac Disease Will Complement the Gluten-Free Diet. Gastroenterology. 2024;167(1):90–103. https://doi.org/10.1053/j.gastro.2024.02.050.
28. Buriánek F., Gege C., Marinković P. New developments in celiac disease treatments. Drug Discov Today. 2024;29(9):104113. https://doi.org/10.1016/j.drudis.2024.104113.
29. Mc Carville J.L., Nisemblat Y., Galipeau H.J., Jury J., Tabakman R., Cohen A. et al. BL-7010 demonstrates specific binding to gliadin and reduces gluten-associated pathology in a chronic mouse model of gliadin sensitivity. PLo S One. 2014;9(11):e109972. https://doi.org/10.1371/journal.pone.0109972.
30. Asri N., Mohammadi S., Jahdkaran M., Rostami-Nejad M., Rezaei-Tavirani M., Mohebbi S.R. Viral infections in celiac disease: what should be considered for better management. Clin Exp Med. 2024;25(1):25. https://doi.org/10.1007/s10238-024-01542-6.
31. Lindeman I., Sollid L.M. Single-cell approaches to dissect adaptive immune responses involved in autoimmunity: the case of celiac disease. Mucosal Immunol. 2022;15(1):51–63. https://doi.org/10.1038/s41385-021-00452-0.
32. Wang Z., Wu Q. Recent advances in the diagnosis of celiac disease. World J Gastroenterol. 2025;31(37):112388. https://doi.org/10.3748/wjg.v31.i37.112388.
33. Robert M.E., Ciacci C., Lebwohl B. Opportunities for Improving Biopsy and Non-Biopsy-Based Diagnosis of Celiac Disease. Gastroenterology. 2024;167(1):79–89. https://doi.org/10.1053/j.gastro.2024.01.031.
