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Journal of Diabetes & Metabolic Disorders

Erschienen in:

05.05.2024 | Research article

Evaluation of genetic association between celiac disease and type 1 diabetes

verfasst von: Sayyad Malekahmadi, Nastaran Asri, Flora Forouzesh, Hedyeh Saneifard, Mostafa Rezaei-Tavirani, Mohammad Rostami-Nejad

Erschienen in: Journal of Diabetes & Metabolic Disorders | Ausgabe 1/2024

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Abstract

Purpose

Celiac disease (CD) is a chronic autoimmune disorder with a common genetic pathogenesis with type 1 diabetes (T1D). This study aimed to investigate the immune regulation in patients with both CD and T1D.

Methods

A total of 29 CD patients, 29 T1D patients, and 16 patients with both CD and T1D, along with 30 healthy controls (HCs) were included. The mRNA expression levels of TNF-α, IL-6, IL-2, and CTLA4 were evaluated in peripheral blood samples.

Results

The results showed that in patients with CD, T1D and CD/T1D, TNF-α mRNA levels were significantly increased (P = 0.0009, 0.0001, and 0.008, respectively), while CTLA4 mRNA levels were significantly decreased in them compared to the control group (P = 0.0009, 0.0001, and 0.004, respectively). IL-2 mRNA expression levels were also significantly higher in CD (P = 0.01) and comorbid CD/T1D (P = 0.01) patients than in the control group. There was no significant difference in terms of IL-6 expression between studied groups (P > 0.05).

Conclusions

TNF-α mRNA exhibited potential diagnostic value for distinguishing CD, T1D, and comorbid CD/T1D patients from HCs. These findings contribute to our understanding of the shared genetic factors and potential mechanisms underlying CD and T1D, which can aid in improved diagnostic methods and treatment approaches for these conditions.

Taraghikhah N, Ashtari S, Asri N, Shahbazkhani B, Al-Dulaimi D, Rostami-Nejad M, et al. An updated overview of spectrum of gluten-related disorders: clinical and diagnostic aspects. BMC Gastroenterol. 2020;20:1–12. https://doi.org/10.1186/s12876-020-01390-0.CrossRef

Rostami-Nejad M, Asri N, Olfatifar M, Khorsand B, Houri H, Rostami K. Systematic review and dose-response meta-analysis on the relationship between different gluten doses and risk of coeliac disease relapse. Nutrients. 2023;15(6):1390. https://doi.org/10.3390/nu15061390.CrossRefPubMedPubMedCentral

Rostami Nejad M, Rostami K, Emami M, Zali M, Malekzadeh R. Epidemiology of celiac disease in Iran: a review. Middle East J Dig Dis. 2011;3(1):5–12.PubMed

Kupper C. Dietary guidelines and implementation for celiac disease. Gastroenterology. 2005;128(4):S121–7. https://doi.org/10.1053/j.gastro.2005.02.024.CrossRefPubMed

Barker JM, Liu E. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr. 2008;55(1):349–65. https://doi.org/10.1016/j.yapd.2008.07.001.CrossRefPubMedPubMedCentral

Cohn A, Sofia AM, Kupfer SS. Type 1 diabetes and celiac disease: clinical overlap and new insights into disease pathogenesis. Curr Diab Rep. 2014;14:1–8. https://doi.org/10.1007/s11892-014-0517-x.CrossRef

Simmons KM, Michels AW. Type 1 diabetes: a predictable disease. World J Diabetes. 2015;6(3):380. https://doi.org/10.4239/wjd.v6.i3.380.CrossRefPubMedPubMedCentral

Farina F, Picascia S, Pisapia L, Barba P, Vitale S, Franzese A, et al. HLA-DQA1 and HLA-DQB1 alleles, conferring susceptibility to celiac disease and type 1 diabetes, are more expressed than non-predisposing alleles and are coordinately regulated. Cells. 2019;8(7):751. https://doi.org/10.3390/cells8070751.CrossRefPubMedPubMedCentral

Rezaei-Tavirani S, Rostami-Nejad M, Vafaee R, Khalkhal E, Keramatinia A, Ehsani-Ardakani MJ, et al. Introducing tumor necrosis factor as a prominent player in celiac disease and type 1 diabetes mellitus. Gastroenterol Hepatol Bed Bench. 2019;12(Suppl1):S123–9.PubMedPubMedCentral

10.

11.

Stephens LA, Thomas HE, Ming L, Grell M, Darwiche R, Volodin L, et al. Tumor necrosis factor-alpha-activated cell death pathways in NIT-1 insulinoma cells and primary pancreatic beta cells. Endocrinology. 1999;140(7):3219–27. https://doi.org/10.1210/endo.140.7.6873.CrossRefPubMed

12.

Zanella I, Paiardi G, Di Lorenzo D, Biasiotto G. Iron absorption in celiac disease and nutraceutical effect of 7-hydroxymatairesinol. Mini-review. Molecules. 2020;25(9):2041. https://doi.org/10.3390/molecules25092041.CrossRefPubMedPubMedCentral

13.

Barartabar Z, Nikzamir A, Sirati-Sabet M, Aghamohammadi E, Chaleshi V, Rostami Nejad M, et al. The relationship between 174 G/C and– 572 G/C of IL-6 gene polymorphisms and susceptibility of celiac disease in the Iranian population. Prz Gastroenterol. 2018;13(4):293–8.PubMedPubMedCentral

14.

Aljada B, Zohni A, El-Matary W. The gluten-free diet for celiac disease and beyond. Nutrients. 2021;13(11):3993. https://doi.org/10.3390/nu13113993.CrossRefPubMedPubMedCentral

15.

Hundhausen C, Roth A, Whalen E, Chen J, Schneider A, Long SA, et al. Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Sci Transl Med. 2016;8(356):ra356119–356119. https://doi.org/10.1126/scitranslmed.aad9943.CrossRef

16.

Lu J, Liu J, Li L, Lan Y, Liang Y. Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets. Clin Translational Immunol. 2020;9(3):e1122. https://doi.org/10.1002/cti2.1122.CrossRef

17.

Meresse B, Korneychuk N, Malamut G, Cerf-Bensussan N. Interleukin-15, a master piece in the immunological jigsaw of celiac disease. Dig Dis. 2015;33(2):122–30. https://doi.org/10.1159/000369521.CrossRefPubMed

18.

Jeker LT, Bour-Jordan H, Bluestone JA. Breakdown in peripheral tolerance in type 1 diabetes in mice and humans. Cold Spring Harbor Perspect Med. 2012;2(3):a007807. https://doi.org/10.1101/cshperspect.a007807.CrossRef

19.

Gerold KD, Zheng P, Rainbow DB, Zernecke A, Wicker LS, Kissler S. The soluble CTLA-4 splice variant protects from type 1 diabetes and potentiates regulatory T-cell function. Diabetes. 2011;60(7):1955–63. https://doi.org/10.2337/db11-0130.CrossRefPubMedPubMedCentral

20.

Hoyne GF, Flening E, Yabas M, Teh C, Altin JA, Randall K, et al. Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to type 1 diabetes. J Immunol. 2011;186(4):2024–32. https://doi.org/10.4049/jimmunol.1002296.CrossRefPubMed

21.

Hunt KA, McGovern DP, Kumar PJ, Ghosh S, Travis SP, Walters JR, et al. A common CTLA4 haplotype associated with coeliac disease. Eur J Hum Genetics: EJHG. 2005;13(4):440–4. https://doi.org/10.1038/sj.ejhg.5201357.CrossRefPubMed

22.

Kayar Y, Dertli R. Association of autoimmune diseases with celiac disease and its risk factors. Pakistan J Med Sci. 2019;35(6):1548. https://doi.org/10.12669/pjms.35.6.821.CrossRef

23.

Nejad MR, Rostami K, Emami MH, Zali MR, Malekzadeh R. Epidemiology of celiac disease in Iran: a review. Middle East J Dig Dis. 2011;3(1):5.

24.

Hagopian W, Lee H-S, Liu E, Rewers M, She J-X, Ziegler A-G et al. Co-occurrence of type 1 diabetes and celiac disease autoimmunity. Pediatrics. 2017;140(5). DOI.

25.

Cartee AK, King KS, Wang S, Dzuris JL, Anderson RP, Van Dyke CT, et al. Plasma IL-2 and symptoms response after acute gluten exposure in subjects with celiac disease or nonceliac gluten sensitivity. Official J Am Coll Gastroenterology| ACG. 2022;117(2):319–26.CrossRef

26.

Lund-Blix NA, Dong F, Mårild K, Seifert J, Barón AE, Waugh KC, et al. Gluten intake and risk of islet autoimmunity and progression to type 1 diabetes in children at increased risk of the disease: the diabetes autoimmunity study in the Young (DAISY). Diabetes Care. 2019;42(5):789–96. https://doi.org/10.2337/dc18-2315.CrossRefPubMedPubMedCentral

27.

Goel G, Tye-Din JA, Qiao S-W, Russell AK, Mayassi T, Ciszewski C, et al. Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Sci Adv. 2019;5(8):eaaw7756.CrossRefPubMedPubMedCentral

28.

Vang T, Congia M, Macis MD, Musumeci L, Orrú V, Zavattari P, et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet. 2005;37(12):1317–9. https://doi.org/10.1038/ng1673.CrossRefPubMed

29.

Parameswaran N, Patial S. Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr. 2010;20(2):87–103. https://doi.org/10.1615/critreveukargeneexpr.v20.i2.10.CrossRefPubMedPubMedCentral

30.

Gogitidze Joy N, Hedrington MS, Briscoe VJ, Tate DB, Ertl AC, Davis SN. Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals. Diabetes care. 2010;33(7):1529-35. DOI.

31.

Lo H-C, Lin S-C, Wang Y-M. The relationship among serum cytokines, chemokine, nitric oxide, and leptin in children with type 1 diabetes mellitus. Clinical biochemistry. 2004;37(8):666– 72. DOI.

32.

Elfaitouri A, Berg AK, Frisk G, Yin H, Tuvemo T, Blomberg J. Recent enterovirus infection in type 1 diabetes: evidence with a novel IgM method. J Med Virol. 2007;79(12):1861–7. https://doi.org/10.1002/jmv.21008.CrossRefPubMed

33.

Vorobjova T, Tagoma A, Oras A, Alnek K, Kisand K, Talja I, et al. Celiac disease in children, particularly with accompanying type 1 diabetes, is characterized by substantial changes in the blood cytokine balance, which may reflect inflammatory processes in the small intestinal mucosa. J Immunol Res. 2019;2019. https://doi.org/10.1155/2019/6179243.

34.

Hunt KA, McGovern DPB, Kumar PJ, Ghosh S, Travis SPL, Walters JRF, et al. A common CTLA4 haplotype associated with coeliac disease. Eur J Hum Genet. 2005;13(4):440–4. https://doi.org/10.1038/sj.ejhg.5201357.CrossRefPubMed

35.

Haseda F, Imagawa A, Murase-Mishiba Y, Sano H, Hirano-Kuwata S, Ueda H, et al. Low CTLA-4 expression in CD4 + helper T-cells in patients with fulminant type 1 diabetes. Immunol Lett. 2011;139(1):80–6. https://doi.org/10.1016/j.imlet.2011.05.003.CrossRefPubMed

36.

Hossen MM, Ma Y, Yin Z, Xia Y, Du J, Huang JY, et al. Current understanding of CTLA-4: from mechanism to autoimmune diseases. Front Immunol. 2023;14. https://doi.org/10.3389/fimmu.2023.1198365.

37.

Freeman HJ. Iron deficiency anemia in celiac disease. World J Gastroenterology: WJG. 2015;21(31):9233. https://doi.org/10.3748/wjg.v21.i31.9233.CrossRefPubMedPubMedCentral

38.

Vincentini O, Maialetti F, Gonnelli E, Silano M. Gliadin-dependent cytokine production in a bidimensional cellular model of celiac intestinal mucosa. Clin Experimental Med. 2015;15:447–54. https://doi.org/10.1007/s10238-014-0325-2.CrossRef

39.

Porpora M, Conte M, Lania G, Bellomo C, Rapacciuolo L, Chirdo FG, et al. Inflammation is present, persistent and more sensitive to proinflammatory triggers in celiac disease enterocytes. Int J Mol Sci. 2022;23(4):1973. https://doi.org/10.3390/ijms23041973.CrossRefPubMedPubMedCentral

Titel: Evaluation of genetic association between celiac disease and type 1 diabetes
verfasst von: Sayyad Malekahmadi
Nastaran Asri
Flora Forouzesh
Hedyeh Saneifard
Mostafa Rezaei-Tavirani
Mohammad Rostami-Nejad
Publikationsdatum: 05.05.2024
Verlag: Springer International Publishing
Erschienen in: Journal of Diabetes & Metabolic Disorders / Ausgabe 1/2024
Elektronische ISSN: 2251-6581
DOI: https://doi.org/10.1007/s40200-024-01429-z

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Evaluation of genetic association between celiac disease and type 1 diabetes