Increased serum levels of quinolinic acid indicate enhanced severity of hepatic dysfunction in patients with liver cirrhosis.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score is a tool for assessment of the degree of hepatic insufficiency/failure. Quinolinic acid (QuinA) is a tryptophan metabolite produced by activated macrophages. Here we investigate whether the degree of systemic inflammation (QuinA, neopterin, CRP and IL-6) correlates with clinical liver dysfunction according to the MELD Score. METHOD: Ninety-four patients with liver cirrhosis were categorized into 2 groups according to baseline MELD score (group I, MELD <20, n = 61, and group II, MELD ≥20, n = 33). RESULTS: Serum levels of QuinA, neopterin, CRP, and IL-6 significantly correlated with MELD score (r = 0.77, 0.75, 0.57, and 0.50; p < 0.0001, respectively). Patients of group II had significantly higher serum levels of QuinA, neopterin, CRP, and IL-6 than group I (p0.0001). ROC curve analysis showed that QuinA and neopterin are more sensitive markers for severity of liver disease than established markers of inflammation such as CRP and IL-6 (sensitivity = 86% and 79%, respectively) (AUC=0.89 and 0.89, respectively). QuinA provided the most sensitive index with regard to the identification of patients with hepatic encephalopathy. CONCLUSION: Serum levels of QuinA reflect the degree of liver dysfunction. Moreover, high levels of QuinA may serve as a sensitive indicator of hepatic encephalopathy.

Strong association of phenylalanine and tryptophan metabolites with activated cytomegalovirus infection in kidney transplant recipients.

Infection-induced inflammation triggers catabolism of proteins and amino acids. Phenylalanine and tryptophan are 2 amino acids related to infections that regulate immune responses. Polyomavirus BK (BKV) and cytomegalovirus (CMV) are important pathogens after kidney transplantation. We investigated the clinical relevance of phenylalanine, tryptophan, and tryptophan metabolites (kynurenine and quinolinic acid) plasma levels in kidney transplant recipients with active CMV (BKV(-)CMV(+), n = 12) or BK virus infection (BKV(+)CMV(-), n = 37). Recipients without active viral infections (CMV(-)BKV(-), n = 28) and CMV(-)BKV(-) healthy individuals (HCs, n = 50) served as controls. In contrast to BKV infection, activated CMV infection is tightly linked to increased phenylalanine and tryptophan metabolite plasma levels (p ≤ 0.002). The association of phenylalanine (cutoff 50 µmol/L) with CMV infection demonstrates high sensitivity (100%) and specificity (94%). By contrast, kynurenine (p = 0.029) and quinolinic acid (p = 0.003) values reflect the severity of CMV infection. In this early proof-of-concept trial, evidence indicates that activated CMV infection is strongly associated with increased phenylalanine as well as kynurenine and quinolinic acid plasma levels. Moreover, tryptophan metabolite levels correlate with disease severity. Measurement of these amino acids is an inexpensive and fast method expected to complete conventional diagnostic assays.

Suppressive dendritic cells as a tool for controlling allograft rejection in organ transplantation: promises and difficulties.

The most important antigen-presenting cells are dendritic cells (DCs), which play a central role in the initiation of immunity and tolerance. Their immunoregulatory properties offer the potential of donor-specific control of graft rejection after organ transplantation. It has not been clarified which DC subpopulations mediate tolerance, and the use of natural DCs for therapeutic applications is therefore problematic. Suppressive DCs can be generated in vitro by treating the cells with biologic, pharmacologic, or genetic agents. Here we discuss approaches for generating inhibitory DCs and present DC-based animal models for control of allograft rejection. A prerequisite of suppressive DCs for therapeutic application in clinical transplantation is a reproducible method for their generation as well as the induction of irreversible suppressive function. Based on lessons learned from the use of DCs as tools in clinical vaccine trials in cancer, we discuss the unknown aspects and risks of DC therapy in transplantation.