Dysregulated expression of T-helper cell responses and susceptibility to infections in high-risk liver transplant recipients

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Background Liver transplant recipients requiring dialysis have poor outcomes including higher risk of infection, and allograft rejection. The role of T-helper cell cytokine responses in the pathogenesis of infections in these patients has not been fully defined. Methods Cases were 11 dialyzed liver transplant recipients. Controls (2 for each case) were patients who were transplanted next to the case but did not require dialysis at any time before or after transplantation. Cytokine responses were assessed in sera collected immediately before transplantation. Data were analyzed for candidate cytokines for pro-inflammatory Th1 (IL-1β, IL-12p70, and IFN-γ), and Th17 (IL-12p40, IL-17), and anti-inflammatory Th2 phenotypes (IL-4, IL-5, IL-10, and IL-13). Results Cases were more likely to have an increase in any of the Th1 or Th1 and Th17 cytokines than the controls ( p = 0.016 and p = 0.04, respectively). Major infections developed in 27% of the study population; these included 46% of the cases and18%, of the controls ( p = 0.09). Patients with infections vs. those without these were more likely to have an increase in any of the Th2 cytokines ( p = 0.005). CMV viremia occurred in 30% of the patients and was significantly associated with Th1 responses even when adjusted for CMV recipient/donor serostatus or any major infection (OR 3.2, 95% CI 0.96–10.73, p = 0.05). Conclusions Requirement of dialysis was characterized by a state of heightened expression of inflammatory responses. However, patients developing infections preferentially expressed Th2 phenotype that may act as a negative regulator of protective inflammatory responses. An enhanced expression of inflammatory mediators may serve to promote CMV infection in liver transplant recipients.