Roles of IL-21 and IL-10 in Celiac Disease Pathogenesis: Case Control Study

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Imad Ahmed Rashid
https://orcid.org/0009-0009-6570-9698
Hind Ahmed Kenoosh
Ezz El-Din Thabet Mahdi

Abstract

Celiac disease (CD) is an immune-mediated enteropathy induced by the ingestion of gluten in genetically predisposed subjects. Although interleukin-21 (IL-21) and interleukin-10 (IL-10) are CD4⁺ T cell-derived cytokines with reciprocal immunological functions, their distinct roles in the pathogenesis of CD remain unclear. This study aimed to measure serum IL-21 and IL-10 levels in patients with celiac disease compared with healthy controls and to analyze their correlation with disease activity. To address this aim, we conducted a case-control study involving 60 biopsy-verified patients with celiac disease and 60 age- and sex-matched healthy controls. We used ELISA to measure IL-21 and IL-10 in the blood. While also recording the levels of anti-tTG antibodies and the Marsh histopathology grades. Our findings revealed that IL-21 and IL-10 levels were significantly higher in CD patients than in controls (IL-21: 31.7 vs. 18.6 pg/mL; IL-10: 14.5 vs. 10.8 pg/mL; p < 0.001 for both). In addition, in patients with CD, IL-21 exhibited a robust positive correlation with anti-tTG titers (ρ = 0.56, p < 0.001) and Marsh grade (ρ = 0.42, p = 0.002), while IL-10 showed no significant associations (all p > 0.05). These findings indicate that although CD is associated with elevated levels of both IL-21 and IL-10, only IL-21 is strongly associated with serological and histopathological markers of active disease. Therefore, these results suggest that an inadequate compensatory anti-inflammatory response is reflected in elevated IL-10 levels, supporting IL-21 as a potential biomarker and therapeutic target in CD.


 

Article Details

How to Cite
Ahmed Rashid, I., Ahmed Kenoosh, H., & Thabet Mahdi , E. E.-D. (2025). Roles of IL-21 and IL-10 in Celiac Disease Pathogenesis: Case Control Study. Tikrit Journal of Pure Science, 31(3), 11–19. https://doi.org/10.25130/tjps.v31i3.2117
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References

1. Makharia GK, Singh P, Catassi C, Sanders DS, Leffler D, Ali RAR, et al. The global burden of coeliac disease: opportunities and challenges. Nature Reviews Gastroenterology & Hepatology. 2022;19(5):313–27. https://doi.org/10.1038/s41575-021-00552-z

2. Leonard MM, Lebwohl B, Rubio-Tapia A, Biagi F. AGA clinical practice update on the evaluation and management of seronegative enteropathies: expert review. Gastroenterology. 2021;160(1):437–44. https://doi.org/10.1053/j.gastro.2020.08.061

3. Singh AD, Ellias S, Singh P, Ahuja V, Makharia GK. The prevalence of celiac disease in patients with dyspepsia: a systematic review and meta-analysis. Digestive Diseases and Sciences. 2022;67(7):3067–79. https://doi.org/10.1007/s10620-021-07142-8

4. Flores-Marin DL, Linden J, Frank E, Pena R, Silvester JA, Therrien A. HLA-DQ7 haplotype among individuals with suspected celiac disease. Digestive and Liver Disease. 2024;56(8):1414–6.https://doi.org/10.1016/j.dld.2024.05.016

5. Persechino F, Galli G, Persechino S, Valitutti F, Zenzeri L, Mauro A, et al. Skin manifestations and coeliac disease in the pediatric population. Nutrients. 2021;13(10):3611.

https://doi.org/10.3390/nu13103611

6. Paolella G, Sposito S, Romanelli AM, Caputo I. Type 2 transglutaminase in coeliac disease: A key player in pathogenesis, diagnosis and therapy. International Journal of Molecular Sciences. 2022;23(14):7513.

https://doi.org/10.3390/ijms23147513

7. Wiarda JE, Loving CL. Intraepithelial lymphocytes in the pig intestine: T cell and innate lymphoid cell contributions to intestinal barrier immunity. Frontiers in Immunology. 2022;13:1048708.

https://doi.org/10.3389/fimmu.2022.1048708

8. Camarca A, Rotondi Aufiero V, Mazzarella G. Role of regulatory T cells and their potential therapeutic applications in celiac disease. International Journal of Molecular Sciences. 2023;24(19):14434. https://doi.org/10.3390/ijms241914434.

9. Shbeer AM, Robadi IA. The role of Interleukin-21 in autoimmune Diseases: Mechanisms, therapeutic Implications, and future directions. Cytokine. 2024;173:156437.

https://doi.org/10.1016/j.cyto.2023.156437

10. Bamidele AO, Mishra SK, Ramos GP, Hirsova P, Klatt EE, Abdelrahman LM, et al. Interleukin 21 Drives a Hypermetabolic State and CD4+ T-Cell–Associated Pathogenicity in Chronic Intestinal Inflammation. Gastroenterology. 2024;166(5):826–41. e19.

https://doi.org/10.1053/j.gastro.2024.01.026

11. Aschenbrenner D, Ye Z, Zhou Y, Hu W, Brooks I, Williams I, et al. Pathogenic Interleukin-10 receptor alpha variants in humans—balancing natural selection and clinical implications. Journal of Clinical Immunology. 2023;43(2):495–511.

https://doi.org/10.1007/s10875-022-01366-7

12. Iversen R, Sollid LM. The immunobiology and pathogenesis of celiac disease. Annual Review of Pathology: Mechanisms of Disease. 2023;18(1):47–70. https://doi.org/10.1146/annurev-pathmechdis-031521-032634

13. Abdukhakimova D, Dossybayeva K, Poddighe D. Fecal and duodenal microbiota in pediatric celiac disease. Frontiers in pediatrics. 2021;9:652208.

https://doi.org/10.3389/fped.2021.652208

14. Kara Y, Eren M, Arslan S, Çilingir O. IL-15 gene polymorphism in celiac disease patients and their siblings. The Turkish Journal of Gastroenterology. 2021;32(4):349.

https://doi.org/10.5152/tjg.2021.19083

15. Shiha MG, Zammit SC, Elli L, Sanders DS, Sidhu R. Updates in the diagnosis and management of coeliac disease. Best Practice & Research Clinical Gastroenterology. 2023;64:101843.

https://doi.org/10.1016/j.bpg.2023.101843

16. Miranda ME, García-Valdés L, Espigares-Rodríguez E, Leno-Durán E, Requena P. Sensibilidad al gluten no celiaca: etiología, diagnóstico diferencial y presentación clínica. Gastroenterología y hepatología. 2023;46(7):562–71. https://doi.org/10.1016/j.gastrohep.2022.10.001

17. Solaymani-Mohammadi S. The IL-21/IL-21R signaling axis regulates CD4+ T-cell responsiveness to IL-12 to promote bacterial-induced colitis. Journal of Leukocyte Biology. 2024;116(4):726–37.

https://doi.org/10.1093/jleuko/qiae069

18. Saadh MJ, Alfattah MA, Ismail AH, Saeed BA, Elashmawy NF, Ismail KS, et al. The role of Interleukin-21 (IL-21) in allergic disorders: biological insights and regulatory mechanisms. International Immunopharmacology. 2024;134:111825. https://doi.org/10.1016/j.intimp.2024.111825

19. Isvoranu G, Chiritoiu-Butnaru M. Therapeutic potential of interleukin-21 in cancer. Frontiers in Immunology. 2024;15:1369743.

https://doi.org/10.3389/fimmu.2024.1369743.