Donor-Derived Fc Gamma Receptor Polymorphisms and Infectious Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation.
Abstract
Background
Delayed immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a major risk factor for infectious complications. Donor-derived genetic variation in immunoregulatory pathways may influence post-transplant immune recovery and susceptibility to infections.
Methods
We analyzed a cohort of 97 adult patients who underwent allo-HSCT. Donor-derived single nucleotide polymorphisms (SNPs) in FCGR2A (rs1801274), FCGR3A (rs396991), FOXP3 (rs3761548), and IL10 (rs1800871) were genotyped using samples demonstrating complete donor chimerism. Associations with engraftment kinetics, immune reconstitution, and infectious complications were evaluated.
Results
Donor-derived IL10-819 non-T/T genotype was associated with earlier neutrophil engraftment and significantly reduced early recovery of total lymphocytes, CD4⁺ T cells, CD8⁺ T cells, and B cells. However, this genotype was not associated with an increased incidence of bacterial, viral, or fungal infections. In contrast, recipients of grafts from donors with the FCGR3A-158 non-F/F genotype exhibited a significantly higher cumulative incidence of fungal infections compared with those receiving grafts from donors with the F/F genotype. No consistent associations were observed between other SNPs and infectious outcomes.
Conclusions
Donor-derived genetic variation in FCGR3A may be associated with an increased risk of fungal infections after allo-HSCT, whereas IL10 polymorphisms appear to influence early immune reconstitution without translating into clinically overt infectious susceptibility. Given the exploration and limited sample size of this study, these findings should be considered hypothesis-generating and warrant validation in larger cohorts.