SCHUMANN RR, LORENZ E, LATZ E, LIMMER N, SCHLAG PM, SCHWARTZ DA; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. B-1107.
Inst. f. Microbiology, Charite Medical Center, Berlin, Germany
BACKGROUND: Recently, the signal transducing receptor for bacterial lipopolysaccharide (endotoxin, LPS) has been identified with the toll-like receptor (TLR) 4. We have demonstrated that two co-segregating missense mutations in human TLR4 frequently occur and are associated with a blunted LPS response in healthy volunteers. To investigate whether these mutations also affect the frequency of septic complications and severity of disease, we analyzed ICU patients regarding TLR4 mutations. METHODS: Eighty-nine surgical ICU patients with a stay of seven or more days or a fatal outcome were studied. DNA was isolated and the region spanning the two known TLR4 mutations was PCR amplified and sequenced to determine the genotype of the patients. Patients were scored for disease severity by APACHE III, and a broad range of clinically relevant parameters. RESULTS: Eleven patients (12.4%) carried the mutations in TLR4. Septic complications occurred significantly more frequently in patients with this TLR4 polymorphism (90.9%) as compared to patients wild-type for TLR4 (53.8%, P=0.02). Initial and maximum APACHE III scores during ICU stay were significantly higher in patients carrying the TLR4 mutations (initial 58.0 versus 45.5, P=0.008, and maximal 61.0 versus 55.0, P=0.04). The odds ratio for septic com-plications for patients with a mutant TLR4 allele was 8.6 (95% confidence interval=1.1-70.2, P=0.02). CONCLUSIONS: Mutations affecting the extracellular domain of TLR4 appear to enhance the risk of septic complications and are associated with a more severe course. These results suggest that the incidence and course of infections in critically ill patients are influenced by relatively common mutations in TLR4.
Publication Types:
Keywords:
- Alleles
- Carrier Proteins
- Critical Illness
- Genotype
- Humans
- Incidence
- Lipopolysaccharides
- Membrane Glycoproteins
- Mutation
- Mutation, Missense
- Polymorphism, Genetic
- Receptors, Cell Surface
- Sepsis
- epidemiology
- genetics
- immunology
Other ID:
UI: 102270498
From Meeting Abstracts