Evaluation of Genetic Association Between Celiac Disease and Type 1 Diabetes

Overview

Journal J Diabetes Metab Disord

Specialty Endocrinology

Date 2024 Jun 27

PMID 38932832

Authors

Sayyad Malekahmadi

Nastaran Asri

Flora Forouzesh

Hedyeh Saneifard

Mostafa Rezaei-Tavirani

Mohammad Rostami-Nejad

Affiliations

Soon will be listed here.

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

Citing Articles

Nutritional Status in Children with Celiac Disease and Type 1 Diabetes Mellitus-A Narrative Review.

Pop D, Ichim E, Farcau D Nutrients. 2025; 17(4).

PMID: 40005056 PMC: 11858457. DOI: 10.3390/nu17040728.

References

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):122-130. DOI: 10.1159/000369521. View

Hagopian W, Lee H, Liu E, Rewers M, She J, Ziegler A . Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity. Pediatrics. 2017; 140(5). PMC: 5654393. DOI: 10.1542/peds.2017-1305. View

Hoyne G, Flening E, Yabas M, Teh C, Altin J, Randall K . 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. DOI: 10.4049/jimmunol.1002296. View

Vang T, Congia M, Macis M, Musumeci L, Orru V, Zavattari P . Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet. 2005; 37(12):1317-9. DOI: 10.1038/ng1673. View

Gerold K, Zheng P, Rainbow D, Zernecke A, Wicker L, 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. PMC: 3121435. DOI: 10.2337/db11-0130. View

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). PMC: 7249079. DOI: 10.3390/molecules25092041. View

Porpora M, Conte M, Lania G, Bellomo C, Rapacciuolo L, Chirdo F . Inflammation Is Present, Persistent and More Sensitive to Proinflammatory Triggers in Celiac Disease Enterocytes. Int J Mol Sci. 2022; 23(4). PMC: 8880034. DOI: 10.3390/ijms23041973. View

Haseda F, Imagawa A, Murase-Mishiba Y, Sano H, Hirano-Kuwata S, Ueda H . Low CTLA-4 expression in CD4+ helper T-cells in patients with fulminant type 1 diabetes. Immunol Lett. 2011; 139(1-2):80-6. DOI: 10.1016/j.imlet.2011.05.003. View

Jeker L, Bour-Jordan H, Bluestone J . Breakdown in peripheral tolerance in type 1 diabetes in mice and humans. Cold Spring Harb Perspect Med. 2012; 2(3):a007807. PMC: 3282496. DOI: 10.1101/cshperspect.a007807. View

10.

Hundhausen C, Roth A, Whalen E, Chen J, Schneider A, Long S . 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):356ra119. PMC: 5125295. DOI: 10.1126/scitranslmed.aad9943. View

11.

Goel G, Tye-Din J, Qiao S, Russell A, Mayassi T, Ciszewski C . Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Sci Adv. 2019; 5(8):eaaw7756. PMC: 6685723. DOI: 10.1126/sciadv.aaw7756. View

12.

Taraghikhah N, Ashtari S, Asri N, Shahbazkhani B, Al-Dulaimi D, Rostami-Nejad M . An updated overview of spectrum of gluten-related disorders: clinical and diagnostic aspects. BMC Gastroenterol. 2020; 20(1):258. PMC: 7409416. DOI: 10.1186/s12876-020-01390-0. View

13.

Cartee A, Choung R, King K, Wang S, Dzuris J, Anderson R . Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity. Am J Gastroenterol. 2021; 117(2):319-326. DOI: 10.14309/ajg.0000000000001565. View

14.

Vorobjova T, Tagoma A, Oras A, Alnek K, Kisand K, Talja I . 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; 2019:6179243. PMC: 6535873. DOI: 10.1155/2019/6179243. View

15.

Barker J, Liu E . Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr. 2008; 55:349-65. PMC: 2775561. DOI: 10.1016/j.yapd.2008.07.001. View

16.

Hossen M, Ma Y, Yin Z, Xia Y, Du J, Huang J . Current understanding of CTLA-4: from mechanism to autoimmune diseases. Front Immunol. 2023; 14:1198365. PMC: 10367421. DOI: 10.3389/fimmu.2023.1198365. View

17.

Vincentini O, Maialetti F, Gonnelli E, Silano M . Gliadin-dependent cytokine production in a bidimensional cellular model of celiac intestinal mucosa. Clin Exp Med. 2014; 15(4):447-54. DOI: 10.1007/s10238-014-0325-2. View

18.

Kayar Y, Dertli R . Association of autoimmune diseases with celiac disease and its risk factors. Pak J Med Sci. 2019; 35(6):1548-1553. PMC: 6861470. DOI: 10.12669/pjms.35.6.821. View

19.

Freeman H . Iron deficiency anemia in celiac disease. World J Gastroenterol. 2015; 21(31):9233-8. PMC: 4541375. DOI: 10.3748/wjg.v21.i31.9233. View

20.

Rostami Nejad M, Rostami K, Yamaoka Y, Mashayekhi R, Molaei M, Dabiri H . Clinical and histological presentation of Helicobacter pylori and gluten related gastroenteropathy. Arch Iran Med. 2011; 14(2):115-8. PMC: 3126917. View