Involvement of the LPS-LPB-CD14-MD2-TLR4 inflammation pathway in HIV-1/HAART-associated lipodystrophy syndrome (HALS).
J Antimicrob Chemother
; 69(6): 1653-9, 2014 Jun.
Article
in En
| MEDLINE
| ID: mdl-24535275
ABSTRACT
OBJECTIVES:
A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS. PATIENTS ANDMETHODS:
This cross-sectional multicentre study involved 558 treated HIV-1-infected patients, 240 with overt HALS and 318 without HALS. Anthropometric, clinical, immunovirological and metabolic variables were determined. Polymorphisms were assessed by genotyping. Plasma levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) whose stored plasma samples were available. Student's t-test, one-way ANOVA, two-way repeated measures ANOVA, the χ(2) test and Pearson and Spearman correlation analyses were carried out for statistical analysis.RESULTS:
LBP rs2232582 TâC polymorphism was significantly associated with HALS (Pâ=â0.01 and Pâ=â0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (Pâ=â0.009) and LBP (Pâ<â0.001) were significantly higher and sCD14 significantly lower (Pâ<â0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (Pâ<â0.001) and hepatitis C virus (Pâ=â0.038), LBP levels by HALS (Pâ<â0.001) and sCD14 levels by age (Pâ=â0.008), current HIV-1 viral load (Pâ=â0.001) and protease inhibitor use (Pâ=â0.018).CONCLUSIONS:
HALS is associated with LBP polymorphism and with higher bacterial translocation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acute-Phase Proteins
/
Membrane Glycoproteins
/
Signal Transduction
/
Carrier Proteins
/
Lipopolysaccharides
/
Lipopolysaccharide Receptors
/
HIV-Associated Lipodystrophy Syndrome
/
Lymphocyte Antigen 96
/
Toll-Like Receptor 4
Type of study:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Antimicrob Chemother
Year:
2014
Document type:
Article
Affiliation country:
Spain