Immunogenomics of hematopoïetic stem cell transplantation

Recipients of allogeneic hematopoïetic stem cell transplantation (HSCT) incur the risk of graft-versus-host disease (GVHD) even when the donor is a sibling who shares the major histocompatibility antigens. Therefore, even the perfect HLA match does not represent the optimal genetic match between donors and recipients in HSCT. In addition to the HLA complex other genetic systems operate and affect the outcome of HSCT. These include minor histocompatibility systems (inducing bona fide allogeneic responses) as well as a series of functional polymorphisms in cytokines and chemokines and receptors genes. Among the items affecting the outcome of HSCT the incidence and severity of infections have an important impact. Polymorphisms of genes controlling both arms of the immune responses to pathogens (innate vs. cognate) are strong candidates for susceptibility factors to infection in allogeneic transplantation. These include the MHC alleles (HLA class I, class II, MIC) CD1, Toll and TLR genes MBP, MPO genes.). In addition to the NK alloreactivity induced by HLA class I epitopes mismatching (a common situation in HSCT) variations in the genotype of the KIR genes may also be encountered between the donor and the recipient leading to potentially harmful or beneficial combinations. An integrated knowledge of the role and hierarchy of the most important genetic factors (MHC and non-MHC) will provide the rationale for a comprehensive matching in HSCT. This short review provides a panorama of this strategic issue for further development of HSCT.