Immune Profile of Mucosal-Associated Invariant T Cells in Chronic Viral Hepatitis: A Systematic Review and Meta-Analysis

Context:

Chronic viral hepatitis (CVH), a world health problem, is the leading cause of hepatocellular carcinoma (HCC). Host immunity plays a critical role in viral clearance, development and progression of the disease. Mucosal-associated invariant T (MAIT) cells represent an abundant form of innate T cells, which plays an essential role in infectious diseases with releasing cytokine, lysing target cells, and shaping adaptive immunity.

Although numerous studies showed the immune profiles of MAIT cells in CVH, the results are inconsistent. Thus, we performed a meta-analysis to analyze the immune profiles of MAIT cells in CVH. Evidence Acquisition: PubMed, Embase, the Cochrane Library, Google Scholar,  ScienceDirect, Web of Science, and the China National Knowledge Infrastructure (CNKI) were searched and 10 studies were included. Data from each study were compared using the standardized mean difference (SMD) with 95% confidence interval (CI). The quality assessment of studies and publication bias were evaluated by Newcastle-Ottawa scale and Begg’s and Egger’s tests, respectively, and a P value of < 0.05 was considered statistically significant.

Meta-analysis of the enrolled studies showed that the frequency of MAIT cells was significantly lower in patients with CVH as compared to healthy controls (SMD = -0.90, 95% CI: -1.32 to -0.48, P < 0.0001). In addition, MAIT cells displayed an activated and exhausted phenotype (CD38: SMD = 0.75, 95% CI: 0.38 to 1.13, P < 0.0001; HLA-DR: SMD = 1.42, 95% CI: 1.02 to 1.83, P < 0.00001; PD-1:SMD = 0.69, 95% CI: 0.13 to 1.26, P = 0.02; CTLA-4: SMD = 0.97, 95% CI: 0.40 to 1.54, P = 0.0008) but not impaired function during CVH (IFN- SMD = 0.04, 95% CI: -0.28 to 0.37, P = 0.79; TNF-: SMD = -0.80, 95% CI: -1.77 to 0.16, P = 0.10; Granzyme B: SMD = -0.14, 95% CI:-0.58 to 0.29, P = 0.53; Perforin: SMD = -0.27, 95% CI: -0.87 to 0.33, P = 0.38).

In CVH patients, MAIT cells are significantly depleted in the peripheral bloodstream and displayed an activated and exhausted phenotype; however, the reduction of peripheral blood MAIT cells accompanied by activated and exhausted phenotypes may not impair the cytolytic function and cytokine production of these cells.