Toll-like receptor polymorphisms in allogeneic hematopoietic cell transplantation

Area of Science:

• Immunogenetics
• Hematopoietic Stem Cell Transplantation

Background:

• Genetic variations in toll-like receptors (TLRs) may influence transplant outcomes.
• Understanding these genetic factors is crucial for improving patient survival after hematopoietic cell transplantation (HCT).

Purpose of the Study:

• To investigate the association between genetic variations in TLRs and outcomes in patients undergoing myeloablative conditioning allogeneic HCT.
• To identify specific TLR single nucleotide polymorphisms (SNPs) that predict transplant success.

Main Methods:

• Genotyped 29 SNPs across 10 TLRs in 816 patient-donor pairs undergoing allogeneic HCT.
• Utilized Bonferroni correction for statistical significance (P ≤ .001).
• Performed survival analyses stratified by donor sex.

Main Results:

• Donor TLR8 rs3764879 (X chromosome) minor allele was significantly associated with outcome (P = .001).
• Male hemizygosity and female homozygosity for the minor allele correlated with poorer disease-free survival (HR, 1.47).
• Further analyses suggested associations with overall survival, disease-free survival, and treatment-related mortality, varying by donor sex.

Conclusions:

• Donor-derived TLR8 rs3764879 minor allele is associated with adverse outcomes after myeloablative allogeneic HCT.
• This genetic marker may help predict transplant success and guide clinical decision-making.
• Further research is warranted to elucidate the mechanisms underlying this association.