Genomic polymorphisms of the innate immune system and allogeneic stem cell transplantation

Abstract

Allogeneic stem cell transplantation (allo-HSCT) is largely employed for treating patients affected by many hematological disorders, but despite the considerable improvement in the treatment of its complications, graft-versus-host disease and infections remain important causes of morbidity and mortality. Innate immunity is crucial in the immune defense against infections after allo-HSCT, and in the biological reactions leading to graft-versus-host disease. Thus, the innate immune system plays an important role in allo-HSCT clinical outcome. It is known now that cytokine gene polymorphisms greatly influence the outcome of allo-HSCT. In addition, genetic variability of some pattern-recognition receptors and antimicrobial peptides represent a promising field to be researched for allo-HSCT impact. Furthermore, more recent work suggests the importance of genetic variability between donor and recipient in the killer cell immunoglobulin-like receptors of the natural killer cells on the allo-HSCT outcome. This article discusses the main cytokines and innate immune gene polymorphisms influencing allo-HSCT outcome, presents new innate immune genes with promising expectations and points at the importance of genetic variability in natural killer cells in allo-HSCT outcome.

Keywords::

• allogeneic stem cell transplantation
• antimicrobial peptides
• graft-versus-host disease
• infection
• innate immune system
• natural killer cell
• pattern-recognition receptor
• polymorphism

Financial & competing interests disclosure

The authors are supported by project PI08/1137 from ISCIII (Instituto de Salud Carlos III), project RD06/0020/0012 from RTICC (Red Temática de Investigación Cooperativa en Cáncer) and project PI0079 from Consejería de Salud, Junta de Andalucía. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

The type of pathogen-associated molecular pattern that causes their activation is indicated for the PRR.

IRF: Interferon regulatory factor; LPS: Lipopolysaccharide; PRR: Pattern recognition receptor; TLR: Toll-like receptor.