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Expression analysis of IL-2, TBX21 and SOCS1 in peripheral blood cells of celiac disease patients reveals the diagnostic potential of IL-2

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Abstract

Background

Celiac disease (CD) is a chronic immune-mediated enteropathy and a cytokine network is involved in its pathogenesis. Interleukin-2 (IL-2) has a key role in the adaptive immune pathogenesis of CD and has been reported to be one of the earliest cytokines to be elicited after gluten exposure by CD patients. This study aimed at investigating the expression level of IL-2 and functionally related genes SOCS1 and TBX21 in active and treated CD patients compared to controls.

Methods and results

Peripheral blood (PB) samples were collected from 40 active CD (ACD), 100 treated CD, and 100 healthy subjects. RNA was extracted, cDNA was synthesized and mRNA expression levels of the desired genes were investigated by Real-time PCR. The gene–gene interaction network was also constructed by GeneMANIA. Our results showed a higher PB mRNA expression of IL-2 in ACD patients compared to controls (p = 0.001) and treated CD patients (p˂0.0001). The mRNA expression level of TBX21 was also significantly up-regulated in ACD patients compared to controls (P = 0.03). SOCS1 mRNA level did not differ between active and treated CD patients and controls (p˃0.05) but showed a significant correlation with the patient’s aphthous stomatitis symptom (r = 0.37, p = 0.01). ROC curve analysis suggested that the use of IL-2 levels can reach a high specificity and sensitivity in discriminating active CD patients.

Conclusions

The PB level of IL-2 has the potential to be introduced as a diagnostic biomarker for CD. Larger cohort studies, including pediatric patients, are needed to achieve more insights in this regard.

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Abbreviations

ACD:

Active celiac disease

B2M:

Beta-2-microglobulin

CD:

Celiac disease

cDNA:

Complementary DNA

GGI:

Gene-gene interaction

HLA:

Human leukocyte antigens

IFN-γ:

interferon gamma

IL:

Interleukin

JAK:

Janus kinase

NCBI:

National Biotechnology Information Center

ONECUT2:

one cut domain family member 2

PB:

Peripheral blood

RNA:

Ribonucleic acid

ROC:

Receiver operating characteristic

SD:

Standard deviation

SOCS1:

Suppressors of cytokine signaling 1

STAT:

Signal transducer and activator of transcription

TBX21:

T-box transcription factor

TFH:

T follicular helper

Th:

T helper

TNF:

Tumor necrosis factor

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Acknowledgements

The authors would like to acknowledge the Gastroenterology and Liver Diseases Research Center of Shahid Beheshti University of Medical Sciences for their support.

Funding

Research reported in this publication was supported by Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Author information

Authors and Affiliations

  1. Department of Cellular and molecular biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Fatemeh Ganjali

  2. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nastaran Asri & Mohammad Rostami-Nejad

  3. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Mehrdad Hashemi

  4. Farhikhtegan Medical Convergence Science Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran

    Mehrdad Hashemi

  5. Department of Vice Chancellor Research Affairs, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Elaheh Ainy

  6. Bambino Gesù Children’s Hospital-IRCCS, Research Laboratories, V.le San Paolo 15, 00146, Rome, Italy

    Andrea Masotti

  7. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hamid Asadzadeh Aghdaei

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  1. Fatemeh Ganjali
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Contributions

Design of experiments by MRN. Analysis of data by NA and FG. First draft of manuscript by FG and EA and subsequent drafting by MRN, MH, AM, NA and HAA. All authors read and approved the final manuscript.

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Correspondence to Mohammad Rostami-Nejad.

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The research was authorized by the Ethics Committee of the Research Institute of Gastroenterology and Liver Diseases of Shahid Beheshti University of Medical Sciences (Ethics code: IR.SBMU.RIGLD.REC.1399.035). Written informed consent was also obtained from participants.

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Ganjali, F., Asri, N., Rostami-Nejad, M. et al. Expression analysis of IL-2, TBX21 and SOCS1 in peripheral blood cells of celiac disease patients reveals the diagnostic potential of IL-2. Mol Biol Rep 50, 4841–4849 (2023). https://doi.org/10.1007/s11033-023-08394-5

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