Infection Complications in Hematopoietic Stem Cells Transplant Recipients: Do Genetics Really Matter?

Abstract

Hematopoietic stem cell transplantation (HSCT) is a highly advanced technique that offers a potential cure for an increasing number of life-threatening diseases. Enormous progress achieved in the last decade, including the refinement of donor selection and advancements in patient supportive care, had significantly improved transplant outcomes; however, invasive infections, graft-vs.-host disease (GVHD) and other serious complications still represent a major source of morbidity and mortality in HSCT recipients. The damage of anatomical barriers due to pre-transplant conditioning, a severely damaged immune function and a profound disruption in the composition of gut microbial commensals (gut microbiota) are alterations inherent to the transplant procedure that are directly implicated in the development of invasive infections and other HSCT complications. Although HLA-matching represents the most important genetic predictor of transplant outcomes, genetic variants in non-HLA genes, especially single nucleotide polymorphisms (SNPs) of genes encoding proteins associated with the immune response to tissue injury and pathogen infection have also been proposed as additional risk factors implicated in the occurrence of HSCT complications. Furthermore, although the microbiota composition is affected by several factors, recent evidence suggests that certain host genetic variants are associated with an altered composition of the gut microbiome and may, therefore, predispose some individuals to invasive infectious complications. This article summarizes the current understanding of the influence that genetic variants in non-HLA genes have on the development of infectious complications in HSCT recipients.

Keywords: GVHD; SNP; cytokine storm; invasive infection; microbiota; stem cells transplantation.

Figure 1

Commensal bacteria of the gut are important modulators of tissue and immune homeostasis (A). The gut microbiota composition is mainly regulated by environmental factors, including diet, use of antibiotics, and the disease status. Host genetics factors appears to contribute to regulate the gut microbiota composition as genetic variations in genes that regulate immune response and genes that directly influence microbiota has been identified. (B) In transplant recipients, the conditioning regimen and the use of antibiotics, induce profound disruption of gut microbiota composition (loss of bacterial diversity, decrease of protective species and outgrowth of pathogenic microorganism), which may result in the development of invasive infections (BSI, pneumonia and clostridium difficile–induced diarrhea). Dysbiosis also contributes to increase the risk to develop transplant complications, such as graft vs. host disease. (C) As the transplant progress, most patients recover the gut microbiota composition (usually by day 60 after transplant), however the presence of transplant complications, massive use of antibiotics may delay the gut microbiota recovery.