Toll-Like Receptor 4 Polymorphisms and Risk of Gram-Negative Bacteremia after Allogeneic Stem Cell Transplantation. A Prospective Pilot Study

The Toll-like receptor 4 (TLR4) gene is a major recognition receptor for lipopolysaccharide (LPS). In a pilot prospective study, we examined the association of 2 TLR4 polymorphisms (Asp299Gly and Thr399Ile) in the donor or the recipient with Gram-negative bloodstream infection (BSI) in 77 allogeneic hematopoietic stem cell transplant (HSCT) patients. Heterozygosity at both loci was defined as “risk genotype.” The cumulative incidence of infection was estimated by treating death prior to infection as a competing risk event and compared between relevant groups using a modified chi-square test. Nine patients had the risk genotype based on donor and 5 based on recipient genotype data. Donor risk genotype showed marginal statistical significance (0.06) in univariate analysis, but not in multivariate analysis. A larger study is required to validate our findings and define genetic susceptibility to this serious infection in HSTC patients.

Key Words: Innate immunity, Toll-like receptor, Mutation, Polymorphism, Gram-negative infection, Bone marrow transplantation