Search

Objectives: Allograft outcome can be improved with the discovery of risk factors that influence adverse events and may allow individualization of patients' treatment. Rejection is the main hurdle to successful transplantation and the immune response is the key effecter to rejection development. Hence, the major objective of the present study was to assess the relationship between single nucleotide polymorphisms (SNPs) in 5 cytokine genes, HLA mismatch and graft outcome in a cohort of 100 Saudi kidney transplant recipients and 100 living related donors at a single transplant center., Materials & Methods: Genotyping of the following positions: TNFA (-308G/A), TGFB1 (codon 10T/C, codon 25C/G), IL-10 (-1082G/A, -819C/T, -592C/A), IL-6 (-174C/G), and IFNG (+874T/A) were performed., Results: The majority of the donors whose recipients presented with either cellular or antibody mediated graft rejection (90% and 100%) respectively were found to be significantly (p=0.0351) associated with intermediate or high IL-10 producing haplotypes, compared to those with stable grafts (58.66%). Haplotypes linked with lower IL-10 production were not detected in the donors or their recipients with antibody mediated graft rejection compared to donors with stable graft (41.33%). The distribution of donor IL-10-1082 haplotypes (GG, GA, AA) showed a statistically significant association of IL-10-1082 GA genotype (p=0.0351) with rejection, when grouped according to patients' rejection status. No other statistically significant deviations were observed in the donors' genotypes. Analyses of cytokine polymorphisms in the recipients revealed no significant association. Multivariate logistic regression analyses showed that only HLA-DRB1 mismatch significantly influenced graft loss (p=0.0135)., Conclusion: This study demonstrates that the donor IL-10 genotypes and HLA-DRB1 mismatch are key determinants in graft outcome after renal transplantation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Extensive allelic matching in the human leukocyte antigen (HLA) genes is regarded as a prerequisite for good clinical success of allogeneic haematopoietic stem cell transplantation (HSCT). Also other genetic factors can be assumed to play a role in preventing and controlling the complications associated with allogeneic HSCT, in particular graft-versus-host disease (GvHD). Interleukin-10 (IL-10) and its receptor (IL-10R), key regulators of the immune response, are among these candidates. We studied the association of IL-10 and IL-10Rbeta gene polymorphisms with the occurrence of GvHD in 309 HLA-identical sibling donor and recipient pairs., Results: The difference in genotypic IL-10 production between patient and donor in combination with patient IL-10Rbeta A/A genotype predisposed strongly to acute GvHD (OR = 7.15, p = 0.000023). On the other hand, a combination of same genotypic IL-10 production with patient IL-10Rbeta A/A genotype protected from chronic GvHD (OR = 0.407, p = 0.0097)., Conclusion: Our results suggest that IL-10 and IL-10Rbeta genes have a synergistic effect on the risk of GvHD.

The ability to positively affect host health through the modulation of the immune response is a feature of increasing importance in measuring the probiotic potential of a bacterial strain. However, the identities of the bacterial cell components involved in cross talk with immune cells remain elusive. In this study, we characterized the dairy strain Lactobacillus helveticus MIMLh5 and its surface-layer protein (SlpA) using in vitro and ex vivo analyses. We found that MIMLh5 and S1pA exert anti-inflamma- tory effects by reducing the activation of NF-κB on the intestinal epithelial Caco-2 cell line. On the contrary, MIMLh5 and S1pA act as stimulators of the innate immune system by triggering the expression of proinflammatory factors tumor necrosis factor alpha and COX-2 in the human macrophage cell line U937 via recognition through Toll-like receptor 2. In the same experiments, SlpA protein did not affect the expression of the anti-inflammatory cytokine interleukin-10. A similar response was observed following stimulation of macrophages isolated from mouse bone marrow or the peritoneal cavity. These results suggest that S1pA plays a major role in mediating bacterial immune-stimulating activity, which could help to induce the host's defenses against and responses toward infections. This study supports the concept that the viability of bacterial cells is not always essential to exert immunomodulatory effects, thus permitting the development of safer therapies for the treatment of specific diseases according to a paraprobiotic intervention. [ABSTRACT FROM AUTHOR]