Gene Expression Profile of Peripheral Blood Monocytes: a Step Towards the Molecular Diagnosis of Celiac Disease?

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Sep 27

PMID 24069342

Citations 13

Authors

Martina Galatola

Valentina Izzo

Donatella Cielo

Marinita Morelli

Giuseppina Gambino

Delia Zanzi

Caterina Strisciuglio

Maria Pia Sperandeo

Luigi Greco

Renata Auricchio

Affiliations

Soon will be listed here.

Abstract

Aim: Celiac disease (CD) is a multifactorial autoimmune disease induced by ingestion of gluten in genetically predisposed individuals. Despite technological progress, the diagnosis of CD is still based on duodenal biopsy as it was 50 years ago. In this study we analysed the expression of CD-associated genes in small bowel biopsies of patients and controls in order to explore the multivariate pathway of the expression profile of CD patients. Then, using multivariant discriminant analysis, we evaluated whether the expression profiles of these genes in peripheral blood monocytes (PBMs) differed between patients and controls.

Participants: Thirty-seven patients with active and 11 with treated CD, 40 healthy controls and 9 disease controls (Crohn's disease patients) were enrolled.

Results: Several genes were differentially expressed in CD patients versus controls, but the analysis of each single gene did not provided a comprehensive picture. A multivariate discriminant analysis showed that the expression of 5 genes in intestinal mucosa accounted for 93% of the difference between CD patients and controls. We then applied the same approach to PBMs, on a training set of 20 samples. The discriminant equation obtained was validated on a testing cohort of 10 additional cases and controls, and we obtained a correct classification of all CD cases and of 91% of the control samples. We applied this equation to treated CD patients and to disease controls and obtained a discrimination of 100%.

Conclusions: The combined expression of 4 genes allows one to discriminate between CD patients and controls, and between CD patients on a gluten-free diet and disease controls. Our results contribute to the understanding of the complex interactions among CD-associated genes, and they may represent a starting point for the development of a molecular diagnosis of celiac disease.

Citing Articles

Gluten consumption and inflammation affect the development of celiac disease in at-risk children.

Auricchio R, Calabrese I, Galatola M, Cielo D, Carbone F, Mancuso M Sci Rep. 2022; 12(1):5396.

PMID: 35354862 PMC: 8968719. DOI: 10.1038/s41598-022-09232-7.

Inflammation Is Present, Persistent and More Sensitive to Proinflammatory Triggers in Celiac Disease Enterocytes.

Porpora M, Conte M, Lania G, Bellomo C, Rapacciuolo L, Chirdo F Int J Mol Sci. 2022; 23(4).

PMID: 35216089 PMC: 8880034. DOI: 10.3390/ijms23041973.

Celiac disease in pediatric patients according to HLA genetic risk classes: a retrospective observational study.

Tolone C, Piccirillo M, Dolce P, Alfiero S, Arenella M, Sarnataro M Ital J Pediatr. 2021; 47(1):107.

PMID: 33952340 PMC: 8097774. DOI: 10.1186/s13052-021-01052-1.

Evaluation of expression of common genes in the intestine and peripheral blood mononuclear cells (PBMC) associated with celiac disease.

Khalkhal E, Nobakht F, Haidari M, Razaghi Z, Ghasemzad M, Sheikhan M Gastroenterol Hepatol Bed Bench. 2021; 13(Suppl1):S60-S67.

PMID: 33585005 PMC: 7881404.

Perturbations in Endocytotic and Apoptotic Pathways Are Associated With Chemotherapy-Induced Nausea.

Singh K, Cao H, Miaskowski C, Conley Y, Hammer M, Wright F Biol Res Nurs. 2020; 23(2):238-247.

PMID: 32815385 PMC: 8822189. DOI: 10.1177/1099800420951271.

References

Gorenne I, Jin L, Yoshida T, Sanders J, Sarembock I, Owens G . LPP expression during in vitro smooth muscle differentiation and stent-induced vascular injury. Circ Res. 2006; 98(3):378-85. DOI: 10.1161/01.RES.0000202802.34727.fd. View

Verhelst K, Carpentier I, Kreike M, Meloni L, Verstrepen L, Kensche T . A20 inhibits LUBAC-mediated NF-κB activation by binding linear polyubiquitin chains via its zinc finger 7. EMBO J. 2012; 31(19):3845-55. PMC: 3463847. DOI: 10.1038/emboj.2012.240. View

Yang L, Anderson D, Baecher-Allan C, Hastings W, Bettelli E, Oukka M . IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature. 2008; 454(7202):350-2. PMC: 2760130. DOI: 10.1038/nature07021. View

Irvine E . Usual therapy improves perianal Crohn's disease as measured by a new disease activity index. McMaster IBD Study Group. J Clin Gastroenterol. 1995; 20(1):27-32. View

Dubois P, Trynka G, Franke L, Hunt K, Romanos J, Curtotti A . Multiple common variants for celiac disease influencing immune gene expression. Nat Genet. 2010; 42(4):295-302. PMC: 2847618. DOI: 10.1038/ng.543. View

Husby S, Koletzko S, Korponay-Szabo I, Mearin M, Phillips A, Shamir R . European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2011; 54(1):136-60. DOI: 10.1097/MPG.0b013e31821a23d0. View

Gibbons D, Abeler-Dorner L, Raine T, Hwang I, Jandke A, Wencker M . Cutting Edge: Regulator of G protein signaling-1 selectively regulates gut T cell trafficking and colitic potential. J Immunol. 2011; 187(5):2067-71. PMC: 3166702. DOI: 10.4049/jimmunol.1100833. View

Abadie V, Discepolo V, Jabri B . Intraepithelial lymphocytes in celiac disease immunopathology. Semin Immunopathol. 2012; 34(4):551-66. DOI: 10.1007/s00281-012-0316-x. View

Vecchi M, Crosti L, Berti E, Agape D, Cerri A, de Franchis R . Increased jejunal intraepithelial lymphocytes bearing gamma/delta T-cell receptor in dermatitis herpetiformis. Gastroenterology. 1992; 102(5):1499-505. DOI: 10.1016/0016-5085(92)91707-b. View

10.

Beitnes A, Raki M, Brottveit M, Lundin K, Jahnsen F, Sollid L . Rapid accumulation of CD14+CD11c+ dendritic cells in gut mucosa of celiac disease after in vivo gluten challenge. PLoS One. 2012; 7(3):e33556. PMC: 3306402. DOI: 10.1371/journal.pone.0033556. View

11.

Hunt K, Zhernakova A, Turner G, Heap G, Franke L, Bruinenberg M . Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet. 2008; 40(4):395-402. PMC: 2673512. DOI: 10.1038/ng.102. View

12.

Sperandeo M, Tosco A, Izzo V, Tucci F, Troncone R, Auricchio R . Potential celiac patients: a model of celiac disease pathogenesis. PLoS One. 2011; 6(7):e21281. PMC: 3132737. DOI: 10.1371/journal.pone.0021281. View

13.

Fina D, Sarra M, Caruso R, Del Vecchio Blanco G, Pallone F, MacDonald T . Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease. Gut. 2007; 57(7):887-92. DOI: 10.1136/gut.2007.129882. View

14.

Orozco L, Bennett B, Farber C, Ghazalpour A, Pan C, Che N . Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages. Cell. 2012; 151(3):658-70. PMC: 3513387. DOI: 10.1016/j.cell.2012.08.043. View

15.

Izzo V, Pinelli M, Tinto N, Esposito M, Cola A, Sperandeo M . Improving the estimation of celiac disease sibling risk by non-HLA genes. PLoS One. 2011; 6(11):e26920. PMC: 3210127. DOI: 10.1371/journal.pone.0026920. View

16.

Sollid L, Jabri B . Triggers and drivers of autoimmunity: lessons from coeliac disease. Nat Rev Immunol. 2013; 13(4):294-302. PMC: 3818716. DOI: 10.1038/nri3407. View

17.

Trynka G, Hunt K, Bockett N, Romanos J, Mistry V, Szperl A . Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat Genet. 2011; 43(12):1193-201. PMC: 3242065. DOI: 10.1038/ng.998. View

18.

Hollis-Moffatt J, Chen-Xu M, Topless R, Dalbeth N, Gow P, Harrison A . Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance. Arthritis Res Ther. 2010; 12(3):R116. PMC: 2911910. DOI: 10.1186/ar3053. View

19.

Maiuri M, De Stefano D, Mele G, Fecarotta S, Greco L, Troncone R . Nuclear factor kappa B is activated in small intestinal mucosa of celiac patients. J Mol Med (Berl). 2003; 81(6):373-9. DOI: 10.1007/s00109-003-0440-0. View

20.

Grunewald T, Pasedag S, Butt E . Cell Adhesion and Transcriptional Activity - Defining the Role of the Novel Protooncogene LPP. Transl Oncol. 2009; 2(3):107-16. PMC: 2730141. DOI: 10.1593/tlo.09112. View