Fas, FasL and Foxp3 gene expression in post-liver transplant autoimmune hepatitis patients with and without acute rejection

Abstract

Aim of the study In this study we investigated Fas, FasL and Foxp3 expression in relation to liver graft rejection and its severity in autoimmune hepatitis (AIH) patients. Material and methods Twenty-three AIH patients including five post-transplant patients with acute rejection (AR) and 18 patients without AR (non-AR) were studied for Fas, FasL and Foxp3 gene expression in peripheral blood mononuclear cells on days 1, 3 and 7 after transplantation by real-time PCR. The relationships between gene expression and clinical features were determined. Results Real-time PCR showed various Fas gene expression levels with no significant difference between the days in AR patients ( p = 0.52). In non-AR patients, Fas level increased from 0.98 ±0.24 fold on the first day to 1.89 ±0.42 fold on day 3 after transplantation ( p < 0.01). In this group of patients, we also found a significant increase in FasL expression on day 7 (29.91 ±6.89 fold) compared to day 1 (13.50 ±7.44 fold, p < 0.05). Foxp3 gene expression in both groups showed decreased levels during the first week after transplantation. The decreased Foxp3 expression in AR patients was correlated with rejection activity index ( r = 0.86, p < 0.0001). Conclusions Increased Fas and FasL gene expression levels in non-AR patients and decreased Foxp3 gene expression in both groups suggested the important role of these molecules in the alloreactive response after liver transplantation in AIH patients. Foxp3 expression might be useful for monitoring rejection severity.

Metabolomics profiling in acute liver transplant rejection in a pediatric population

“…Previous research involving tryptophan metabolism as a significant metabolite hypothesized that rejection-specific pathways are linked to immune T cells modulation and the role of nutrients in their functioning 16 , 17 . This could be important as the link between T cells and other nutrients is a two-way street, where the activation of T cells requires the metabolism of other molecules, mainly amino acids such as leucine, and the flux of glucose, lactate, lipids, proteins, nucleic acids and carbohydrates requires activated T cells 18 , 19 . Furthermore, the role of immune T cells is also linked to the metabolism of the amino acid tryptophan, which is one of the two prominent pathways we distinguished.…”

Immunological Determinants of Liver Transplant Outcomes Uncovered by the Rat Model

“… 119 Pharmacological and immunological treatments that favor in vivo expansion of this population are also being considered. 119 , 121 - 123 …”

“…119 Pharmacological and immunological treatments that favor in vivo expansion of this population are also being considered. 119,[121][122][123] Myeloid-derived DCs (mDCs) in the liver microenvironment differentiate into a more tolerogenic phenotype. The presence of hepatocyte growth factor upregulates IL-10 expression by DCs monocytes 16 and the strong interaction established between Ag-specific T reg and DCs can result in the removal of the MHC-antigen complex from the surface of the DCs, compromising their ability to present antigens.…”