The role of bacteria and pattern recognition receptors in GVHD

E Holler, K Landfried, J Meier, M Hausmann, G Rogler, E Holler, K Landfried, J Meier, M Hausmann, G Rogler

Abstract

Graft-versus-Host Disease (GvHD) is the most serious complication of allogeneic stem cell transplantation (SCT) and results from an activation of donor lymphocytes by recipient antigen-presenting cells (APCs). For a long time, it has been postulated that the intestinal microflora and endotoxin exert a crucial step in this APC activation, as there is early and severe gastrointestinal damage induced by pretransplant conditioning. With the detailed description of pathogen-associated molecular patterns and pathogen recognition receptors single nucleotide polymorphisms of TLRs and especially NOD2 have been identified as potential risk factors of GvHD and transplant related complications thus further supporting the crucial role of innate immunity in SCT, related complications. Gastrointestinal decontamination and neutralization of endotoxin have been used to interfere with this early axis of activation with some success but more specific approaches of modulation of innate immunity are needed for further improvement of clinical outcome.

Figures

Figure 1
Figure 1
Treatment-related mortality and SNPs of innate immunity. SNPs 8,12 and 13 of NOD2 (n = 358) and the T300A. SNP of ATG16L1 (n = 127) were assessed by PCR in patients receiving allogeneic SCT and their respective HLA-identical sibling donors. Cumulative treatment related mortality as calculated by Kaplan-Meier method is shown in relation to absence of any SNPs (wt, wild-type) or presence of SNPs (variant, var) in recipients (R) and/or donors (D). Both associations were significant by log rank tests (P = .003 for NOD2, P = .03 for ATG16L1).

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