Blood, 1 December 2002, Vol. 100, No. 12, pp. 3851-3852
HLA immunogenetics in hematopoietic stem cell
transplantation
Recent research has suggested that non-HLA immunogenetics, in
particular cytokine gene polymorphisms, play an important role in the
outcome of HLA-matched sibling transplantations including graft-versus-host disease (GVHD) and transplant-related
mortality. More recently the gene polymorphisms for the mannose-binding
lectin (Mullighan et al, Blood. 2002;99:3524-3529) have been shown
to be associated with infection in a heterogeneous cohort of allogeneic hematopoietic stem cell transplantation (SCT) patients. Bacterial and fungal infections, as well as GVHD, are the most life-threatening factors following SCT. Improved individual patient supportive care
including modified prophylaxis and immunosuppression may be possible
with the use of a genetic risk-factor analysis by identifying those
patients at greatest risk of SCT complications due to either their own
or their donor's genotype. The polymorphisms of the gene under study
often occur within the promoter regions of the gene giving rise, for
example, to individual genotypically determined high or low levels of
the cytokine or high or low levels of enzyme activity.
In a unique study, Rocha and colleagues (page 3908) have elegantly
identified patient and donor inflammatory and host-defense genetic risk
factors associated with neutrophil recovery and bacterial infections.
Donor genetic risk factors influencing bacterial infections were
identified by the study of myeloperoxidase gene (MPO)
polymorphisms (
463A>G polymorphism). The cumulative
incidence of at least one bacterial infection was assessed at day 180 after SCT. The cumulative incidence for MPO donor genotype AG
was 38%, and for AA 50%, compared with 20% in the negative-risk
donor genotype of GG. The MPO donor risk genotype (AG or AA) may
reflect the decreased enzymatic activities of MPO present in
engrafted neutrophils. The AA genotype was also associated with the
risk of nonleukemic death.
The Fc
RIIIb genotype of the donor was also associated with a delay
in time to neutrophil recovery and risk of early death. Rocha et al
further confirmed earlier studies of our own on the protective role of
donor IL-1 receptor antagonist genotype in acute GVHD. Their
study of a homogeneous population of transplantation patients using
multifactorial analysis further strengthens the importance of non-HLA
immunogenetics in allogeneic SCT. The results form the basis of further
studies on the mechanism of activity of host defense against infection
and, in addition to other genetic risk-factor analyses, may aid in both
choice of donor and establishing new SCT prophylactic and therapeutic strategies.
Anne M. Dickinson
University of Newcastle
