Cover Image

The Screening of Critical Related Genes in Celiac Disease Based on Intraepithelial Lymphocytes Investigation: A Bioinformatics Analysis

Mohammad Rostami-Nejad, Reza vafaee, Mohammad Javad Ehsani-Ardakani, Nika Aghamohammadi, Aliasghar Keramatinia, Saeed Abdi, Hamideh Moravvej

Background: Celiac disease (CD) is an immunological intestinal disorder, which is characterized by response to gluten. In addition to the environmental factors and dysbiosis of the gut microbiota, genetic susceptibility has an important role in the pathogenesis of this multifactorial disorder. Therefore, this study aims to present the crucial involved genes in CD pathogenesis. Materials and Methods: In this bioinformatics analysis study, significant differentially expressed genes of intraepithelial lymphocytes (IELs) samples of celiac patients versus normal patients from Gene Expression Omnibus (GEO) database were screened via the protein-protein interaction (PPI) network. The critical nodes based on degree values, betweenness centrality, and fold changes were determined and enriched by ClueGO to find relative biological terms. Results: According to the network analysis, five central nodes including IL2, PIK3CA, PRDM10, AKT1, and SRC and eight significant differentially expressed genes (DEGs) were determined as the critical genes related to CD. Also, CD4+, CD25+, alpha-beta regulatory T cell differentiation are identified as prominent biological terms in the celiac disease patients. Conclusion: There is a possible biomarker panel related to CD that can be used as a therapeutic or diagnostic tool to manage the disease. [GMJ.2019;8:e1407]

Celiac Disease; Gene; Network; Biomarker

Rostami Nejad M, Rostami K, Cheraghipour K, Nazemalhosseini Mojarad E, Volta U, Al Dulaimi D, Zali MR. Celiac disease increases the risk of Toxoplasma gondii infection in a large cohort of pregnant women. Am J Gastroenterol. 2011;106(3):548-9.


Rostami Nejad M, Karkhane M, Marzban A, Nazemalhosseini Mojarad E, Rostami K. Gluten related disorders. Gastroenterol Hepatol Bed Bench. 2012 Winter;5(Suppl 1):S1-7.

Parra-Medina R, Molano-Gonzalez N, Rojas-Villarraga A, Agmon-Levin N, Arango M-T, Shoenfeld Y, et al. Prevalence of celiac disease in Latin America: a systematic review and meta-regression. PLoS One. 2015;10(5):e0124040.

PMid:25942408 PMCid:PMC4420463

Rostami-Nejad M, Romanos J, Rostami K, Ganji A, Ehsani-Ardakani MJ, Bakhshipour AR, Zojaji H, Mohebbi SR, Zali MR, Wijmenga C. Allele and haplotypefrequencies for HLA-DQ in Iranian celiac disease patients. World J Gastroenterol. 2014 May 28;20(20):6302-8.

PMid:24876751 PMCid:PMC4033468

Nilsen E, Gjertsen H, Jensen K, Brandtzaeg P, Lundin K. Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern in both coeliac patients and controls. Clin Exp Immunol. 1996;103(2):295-303.

PMid:8565315 PMCid:PMC2200356

Caputo I, Barone MV, Martucciello S, Lepretti M, Esposito C. Tissue transglutaminase in celiac disease: role of autoantibodies. Amino acids. 2009;36(4):693-9.


Parzanese I, Qehajaj D, Patrinicola F, Aralica M, Chiriva-Internati M, Stifter S, et al. Celiac disease: From pathophysiology to treatment. World J Gastrointest Pathophysiol. 2017;8(2):27.

PMid:28573065 PMCid:PMC5437500

Marsh MN, Crowe PT. Morphology of the mucosal lesion in gluten sensitivity. Baillieres Clin Gastroenterol. 1995;9(2):273-93.

Bagdi E, Diss TC, Munson P, Isaacson PG. Mucosal intra-epithelial lymphocytes in enteropathy-associated T-cell lymphoma, ulcerative jejunitis, and refractory celiac disease constitute a neoplastic population. Blood. 1999;94(1):260-4.

De Re V, Simula MP, Canzonieri V, Cannizzaro R. Proteomic analyses lead to a better understanding of celiac disease: focus on epitope recognition and autoantibodies. Dig Dis Sci. 2010;55(11):3041-46.


Azodi MZ, Peyvandi H, Rostami-Nejad M, Safaei A, Rostami K, Vafaee R, et al. Protein-protein interaction network of celiac disease. Gastroenterol Hepatol Bed Bench. 2016;9(4): 268-277.

Rezaei-Tavirani M, Rezaei-Tavirani S, Ahmadi N, Naderi N, Abdi S. Pancreatic adenocarcinoma protein-protein interaction network analysis. Gastroenterol Hepatol Bed Bench. 2017 Winter;10 (Suppl1):S85-S92.

Tavirani MR, Mansouri V, Tavirani SR, Tackallou SH, Rostami-Nejad M. Gliosarcoma Protein-Protein Interaction Network Analysis and Gene OntologyInt J Cancer Manag. I2018:e65701.

Stulík J, Hernychová L, Porkertová S, Pozler O, Tučková L, Sánchez D, et al. Identification of new celiac disease autoantigens using proteomic analysis. Proteomics. 2003;3(6):951-6.


Zhang L, Nabel GJ. Positive and negative regulation of IL-2 gene expression: role of multiple regulatory sites. Cytokine. 1994;6(3):221-8.

Nilsen EM, Jahnsen FL, Lundin KE, Johansen FE, Fausa O, Sollid LM, et al. Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology. 1998;115(3):551-63.

Vojtěchová M, Turečková J, Kučerová D, Šloncová E, Vachtenheim J, Tuháčková Z. Regulation of mTORC1 signaling by Src kinase activity is Akt1-independent in RSV-transformed cells. Neoplasia. 2008;10(2):99-107.

PMid:18283331 PMCid:PMC2244684

Di Zazzo E, De Rosa C, Abbondanza C, Moncharmont B. PRDM proteins: molecular mechanisms in signal transduction and transcriptional regulation. Biology. 2013;2(1):107-41.

PMid:24832654 PMCid:PMC4009873

Batoon L, Millard SM, Raggatt LJ, Pettit AR. Osteomacs and bone regeneration. Current osteoporosis reports. 2017;15(4):385-95.


Vasiliou V, Nebert DW. Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family. Hum Genomics. 2005;2(2):138-43.

PMid:16595077 PMCid:PMC3500182

Arentz-Hansen H, Körner R, Molberg Ø, Quarsten H, Vader W, Kooy YM, et al. The intestinal T cell response to α-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med. 2000;191(4):603-12.

PMid:10684852 PMCid:PMC2195837

Anderson RP, Degano P, Godkin AJ, Jewell DP, Hill AV. In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope. Nature Med. 2000;6(3):337.


Jabri B, Sollid LM. T cells in celiac disease. J Immunol. 2017;198(8):3005-14.

PMid:28373482 PMCid:PMC5426360


  • There are currently no refbacks.