Toll-Like 4 Receptor Variant, Asp299Gly, and Reduced Risk of Hemorrhagic Cystitis after Hematopoietic Stem Cell Transplantation

3Citations
Citations of this article
10Readers
Mendeley users who have this article in their library.

Abstract

Hemorrhagic cystitis (HC) is a major cause of morbidity after hematopoietic stem cell transplantation. Toll-like receptor 4 (TLR4) is a pattern recognition receptor of the innate immune system and induces inflammation. Individuals with the single nucleotide polymorphisms Thr399Ile (rs4986791) or Asp299Gly (rs4986790) of TLR4 show diminished inflammatory responsiveness to endotoxins. The genotype of TLR4 was determined in 166 children who underwent allogeneic hematopoietic stem cell transplantation and in their donors. Asp299Gly was present in 21 patients (13%) and 24 donors (14%). Thr399Ile was found in 22 patients (13%) and 25 donors (15%). The incidence of HC was significantly lower in patients with Asp299Gly (0% vs 23%; . P = .009) and in patients who underwent transplantation from a donor with Asp299Gly (4% vs 23%; . P = .05). The trend was the same for Thr399Ile-donor positive (8% vs 22%; . P = .17), recipient positive (9% vs 22%; . P = .25), donor or recipient positive (8% vs 23%; . P = .04). Multivariate analysis revealed age, conditioning with busulfan, and absence of Asp299Gly as independent risk factors for HC. In conclusion, the TLR4 Asp299Gly variant seems to confer protection against hemorrhagic cystitis. This study provides the first indication that the innate immune system through TLR4 signaling pathway plays a role in the pathogenesis of HC after hematopoietic stem cell transplantation. © 2012 American Society for Blood and Marrow Transplantation.

Cite

CITATION STYLE

APA

Gruhn, B., Klöppner, N., Pfaffendorf-Regler, N., Beck, J., Zintl, F., Bartholomä, S., … Steinbach, D. (2012). Toll-Like 4 Receptor Variant, Asp299Gly, and Reduced Risk of Hemorrhagic Cystitis after Hematopoietic Stem Cell Transplantation. Biology of Blood and Marrow Transplantation, 18(6), 958–963. https://doi.org/10.1016/j.bbmt.2012.01.018

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free