Linked Life Data

11529488

Source:http://linkedlifedata.com/resource/pubmed/id/11529488

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2001-8-31
pubmed:abstractText
Lipopolysaccharide (LPS) has been implicated in the pathogenesis of graft-versus-host disease (GVHD). The toll-like receptor (TLR)-4 has been recently identified as a major receptor for LPS. Mutations of TLR4 have been associated with LPS hyporesponsiveness. We hypothesized that TLR4 mutations reduce the risk of acute GVHD in allogeneic marrow transplant recipients. In a preliminary study to determine the frequency of TLR4 mutations and their possible association with GVHD, we tested 237 patients and their HLA-identical sibling donors for 2 TLR4 polymorphisms. All patients received methotrexate and cyclosporine for GVHD prophylaxis. One or more mutants were detected in 10.8% of patients and 10.6% of donors. Multivariable logistic regression models were used to analyze the association between TLR4 mutations and probability (1-sided) of GVHD. The odds ratio (adjusted for advanced disease, total body irradiation dose, and patient age) for development of grades II to IV GVHD when a mutation was present in the recipient was 0.63 (95% confidence interval [CI], 0.25-1.60; P = .16). When a mutation was present in the donor, the adjusted odds ratio was 0.88 (95% CI, 0.36-2.17; P = .40). When a mutation was present in both recipient and donor, the odds ratio was 0.72 (95% CI, 0.22-2.32; P = .29). Among 24 patients with TLR4 mutations in either donor or recipient, 4 (16.7%) developed gram-negative bacteremia. Among 213 patients without mutations, 14 (6.6%) developed gram-negative bacteremia (P = .09). The data indicate that a reduced risk of acute GVHD is associated with TLR4 mutations and that TLR4 mutations may increase the risk for gram-negative bacteremia. However, these associations are not statistically significant in recipients of HLA-matched sibling marrow transplants who are prophylactically treated for infections and GVHD. A much larger study population would be needed to confirm the role of LPS in the pathogenesis of GVHD in humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1083-8791
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
384-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11529488-Bacteremia, pubmed-meshheading:11529488-Cohort Studies, pubmed-meshheading:11529488-Drosophila Proteins, pubmed-meshheading:11529488-Gene Frequency, pubmed-meshheading:11529488-Genetic Testing, pubmed-meshheading:11529488-Graft vs Host Disease, pubmed-meshheading:11529488-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:11529488-Histocompatibility Testing, pubmed-meshheading:11529488-Humans, pubmed-meshheading:11529488-Lipopolysaccharides, pubmed-meshheading:11529488-Membrane Glycoproteins, pubmed-meshheading:11529488-Mutation, pubmed-meshheading:11529488-Nuclear Family, pubmed-meshheading:11529488-Odds Ratio, pubmed-meshheading:11529488-Prospective Studies, pubmed-meshheading:11529488-Receptors, Cell Surface, pubmed-meshheading:11529488-Risk Factors, pubmed-meshheading:11529488-Toll-Like Receptor 4, pubmed-meshheading:11529488-Toll-Like Receptors, pubmed-meshheading:11529488-Transplantation, Homologous
pubmed:year
2001
pubmed:articleTitle
Association of TLR4 mutations and the risk for acute GVHD after HLA-matched-sibling hematopoietic stem cell transplantation.
pubmed:affiliation
Department of Medicine, Duke University, Durham, North Carolina, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.