Significance of MAIT Cells in Inflammatory Bowel Disease

Not yet recruiting

• Conditions: Inflammatory Bowel Diseases

• Registration Number: NCT05598346
• Lead Sponsor: Assiut University

Brief Summary

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

Detailed 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.

Study Timeline

• Study First Submitted: 2022-10-25
• Study First Submitted QC: 2022-10-25
• Study First Posted: 2022-10-28
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-09
• Last Update Posted: 2022-11-14
• Study Start: 2023-03-01
• Primary Completion: 2024-03
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 70

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

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Detection of MAIT cells level in IBD,Compare its level with disease activity	Baseline	Monoclonal Antibodies by flow cytometry used for detection of MAIT cells in IBD patients