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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05598346
Other study ID # MAIT cells in In IBD
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date March 1, 2023
Est. completion date April 2024

Study information

Verified date November 2022
Source Assiut University
Contact AL- shimaa mohamed salahidden
Phone 01010328330
Email shoshomylife86@gmail.com
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

To examine the level and function of MAIT cells in IBD patients, and to compare it with disease activity.


Description:

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory diseases of unknown origin. IBD has become a global disease with increasing incidence in newly industrialized and westernized countries. Genetic and environmental factors with inadequate host immune response to gut flora appear to play important roles in the pathogenesis of IBD. Adaptive immune response has been classically considered to play a major role in IBD pathogenesis . Infiltrating lymphocytes including T helper (Th) 1 cells and Th17 cells can lead to the development of intestinal lesions . However, recent evidences suggest that innate immune response is equally important in inducing gut inflammation . Altered epithelial barrier function and aberrant innate immune responses contribute to intestinal inflammation in IBD patients. Mucosal-associated invariant T (MAIT) cells are innate lymphocytes that express a conserved invariant Tcell receptor (TCR) Vα7.2-Jα33 chain paired with a limited set of Vβ chains. Using distinct pairs of TCR chains, MAIT cells can recognize bacteria-derived riboflavin (vitamin B2) metabolites presented by MHC(major histocompatibility complex) class 1b-like related protein (MR1). Upon MR1-dependent recognition of antigens, MAIT cells are activated to rapidly release Th1/Th17 proinflammatory cytokines (i.e., interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and interleukin [IL]-17 and cytotoxic molecules (i.e.,granzyme and perforin) to kill infected host cells. MAIT cells are abundant in peripheral blood where they where they express gut-homing chemokine receptors such as CCR6(chemokine receptor type 6) and CCR9(chemokine receptor type9). They are also abundant in intestinal mucosa where they likely confront normal flora or pathogenic bacteria producing bacterial ligands. Given tissue- homing properties and rapid production of proinflammatory cytokines, MAIT cells may play an important role in infectious diseases and autoimmune disorders. Results from experiment with transfer of MAIT cells to TNBS(trinitrobenzene sulfonic acid)-induced IBD murine models suggest that MAIT cells might play a protective role in TNBS-induced intestinal inflammation . In addition, previous studies have reported MAIT cell dysfunction in IBD patients. However, the role of MAIT cells in IBD patients remains unclear.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 70
Est. completion date April 2024
Est. primary completion date March 2024
Accepts healthy volunteers
Gender All
Age group 15 Years to 50 Years
Eligibility Inclusion Criteria: - Patients with active IBD according to clinical scores with the following: 1. Recently discovered. 2. Average age (15-50). Exclusion Criteria: - Patient with history of any of the following ; 1. History of respiratory disorders such as chronic obstructive diseases, pulmonary disease or pulmonary embolism. 2. Other Autoimmune diseases, infectious diseases. 3. Recent surgery, malignancies, left ventricular dysfunction, use of immunosuppressive drugs. 4. Chronic liver, renal, and endocrine diseases.

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Assiut University

References & Publications (26)

Cho YN, Kee SJ, Kim TJ, Jin HM, Kim MJ, Jung HJ, Park KJ, Lee SJ, Lee SS, Kwon YS, Kee HJ, Kim N, Park YW. Mucosal-associated invariant T cell deficiency in systemic lupus erythematosus. J Immunol. 2014 Oct 15;193(8):3891-901. doi: 10.4049/jimmunol.130270 — View Citation

Cosgrove C, Ussher JE, Rauch A, Gärtner K, Kurioka A, Hühn MH, Adelmann K, Kang YH, Fergusson JR, Simmonds P, Goulder P, Hansen TH, Fox J, Günthard HF, Khanna N, Powrie F, Steel A, Gazzard B, Phillips RE, Frater J, Uhlig H, Klenerman P. Early and nonrever — View Citation

Dusseaux M, Martin E, Serriari N, Péguillet I, Premel V, Louis D, Milder M, Le Bourhis L, Soudais C, Treiner E, Lantz O. Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood. 2011 Jan 27;117(4):1250-9. doi: 10 — View Citation

Feagan BG, Sandborn WJ, D'Haens G, Panés J, Kaser A, Ferrante M, Louis E, Franchimont D, Dewit O, Seidler U, Kim KJ, Neurath MF, Schreiber S, Scholl P, Pamulapati C, Lalovic B, Visvanathan S, Padula SJ, Herichova I, Soaita A, Hall DB, Böcher WO. Induction — View Citation

Fonseca-Camarillo G, Yamamoto-Furusho JK. Immunoregulatory Pathways Involved in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2015 Sep;21(9):2188-93. doi: 10.1097/MIB.0000000000000477. Review. — View Citation

Gajendran M, Loganathan P, Catinella AP, Hashash JG. A comprehensive review and update on Crohn's disease. Dis Mon. 2018 Feb;64(2):20-57. doi: 10.1016/j.disamonth.2017.07.001. Epub 2017 Aug 18. Review. — View Citation

Garrett WS, Gordon JI, Glimcher LH. Homeostasis and inflammation in the intestine. Cell. 2010 Mar 19;140(6):859-70. doi: 10.1016/j.cell.2010.01.023. Review. — View Citation

Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev. 2014 Jan;13(1):3-10. doi: 10.1016/j.autrev.2013.06.004. Epub 2013 Jun 15. Review. — View Citation

Giuffrida P, Corazza GR, Di Sabatino A. Old and New Lymphocyte Players in Inflammatory Bowel Disease. Dig Dis Sci. 2018 Feb;63(2):277-288. doi: 10.1007/s10620-017-4892-4. Epub 2017 Dec 23. Review. — View Citation

Grimaldi D, Le Bourhis L, Sauneuf B, Dechartres A, Rousseau C, Ouaaz F, Milder M, Louis D, Chiche JD, Mira JP, Lantz O, Pène F. Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections. Intensive Care — View Citation

Jiang J, Wang X, An H, Yang B, Cao Z, Liu Y, Su J, Zhai F, Wang R, Zhang G, Cheng X. Mucosal-associated invariant T-cell function is modulated by programmed death-1 signaling in patients with active tuberculosis. Am J Respir Crit Care Med. 2014 Aug 1;190( — View Citation

Kim JC, Jin HM, Cho YN, Kwon YS, Kee SJ, Park YW. Deficiencies of Circulating Mucosal-associated Invariant T Cells and Natural Killer T Cells in Patients with Acute Cholecystitis. J Korean Med Sci. 2015 May;30(5):606-11. doi: 10.3346/jkms.2015.30.5.606. E — View Citation

Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, Bhati M, Chen Z, Kostenko L, Reantragoon R, Williamson NA, Purcell AW, Dudek NL, McConville MJ, O'Hair RA, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, McCluskey J. MR1 presents micro — View Citation

Kwon YS, Cho YN, Kim MJ, Jin HM, Jung HJ, Kang JH, Park KJ, Kim TJ, Kee HJ, Kim N, Kee SJ, Park YW. Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity. Tube — View Citation

Le Bourhis L, Martin E, Péguillet I, Guihot A, Froux N, Coré M, Lévy E, Dusseaux M, Meyssonnier V, Premel V, Ngo C, Riteau B, Duban L, Robert D, Huang S, Rottman M, Soudais C, Lantz O. Antimicrobial activity of mucosal-associated invariant T cells. Nat Im — View Citation

Leeansyah E, Ganesh A, Quigley MF, Sönnerborg A, Andersson J, Hunt PW, Somsouk M, Deeks SG, Martin JN, Moll M, Shacklett BL, Sandberg JK. Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HI — View Citation

Meierovics A, Yankelevich WJ, Cowley SC. MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):E3119-28. doi: 10.1073/pnas.1302799110. Epub 2013 Jul 29. — View Citation

Meierovics AI, Cowley SC. MAIT cells promote inflammatory monocyte differentiation into dendritic cells during pulmonary intracellular infection. J Exp Med. 2016 Nov 14;213(12):2793-2809. Epub 2016 Oct 31. — View Citation

Miyazaki Y, Miyake S, Chiba A, Lantz O, Yamamura T. Mucosal-associated invariant T cells regulate Th1 response in multiple sclerosis. Int Immunol. 2011 Sep;23(9):529-35. doi: 10.1093/intimm/dxr047. Epub 2011 Jun 28. — View Citation

Napier RJ, Adams EJ, Gold MC, Lewinsohn DM. The Role of Mucosal Associated Invariant T Cells in Antimicrobial Immunity. Front Immunol. 2015 Jul 6;6:344. doi: 10.3389/fimmu.2015.00344. eCollection 2015. Review. — View Citation

Ruijing X, Mengjun W, Xiaoling Z, Shu P, Mei W, Yingcheng Z, Yuling H, Jinquan T. Ja33+ MAIT cells play a protective role in TNBS induced intestinal inflammation. Hepatogastroenterology. 2012 May;59(115):762-7. doi: 10.5754/hge11432. — View Citation

Serriari NE, Eoche M, Lamotte L, Lion J, Fumery M, Marcelo P, Chatelain D, Barre A, Nguyen-Khac E, Lantz O, Dupas JL, Treiner E. Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases. Clin Exp Immunol. 2014 May;17 — View Citation

Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F, Affaticati P, Gilfillan S, Lantz O. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature. 2003 Mar 13;422(6928):164-9. Erratum in: Nature. 2003 Jun 26; — View Citation

Walsh AJ, Ghosh A, Brain AO, Buchel O, Burger D, Thomas S, White L, Collins GS, Keshav S, Travis SP. Comparing disease activity indices in ulcerative colitis. J Crohns Colitis. 2014 Apr;8(4):318-25. doi: 10.1016/j.crohns.2013.09.010. Epub 2013 Oct 10. — View Citation

Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007 Jul 26;448(7152):427-34. Review. — View Citation

Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol. 2014 Jan 7;20(1):91-9. doi: 10.3748/wjg.v20.i1.91. Review. — View Citation

* Note: There are 26 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Detection of MAIT cells level in IBD,Compare its level with disease activity Monoclonal Antibodies by flow cytometry used for detection of MAIT cells in IBD patients Baseline
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