Involvement of the LPS-LPB-CD14-MD2-TLR4 inflammation pathway in HIV-1/HAART-associated lipodystrophy syndrome (HALS)
Por:
Vilades, C, Escote, X, Lopez-Dupla, M, Martinez, E, Domingo, P, Asensi, V, Leal, M, Peraire, J, Inza, MI, Arnedo, M, Gutierrez, M, Valle-Garay, E, Ferrando-Martinez, S, Olona, M, Alba, V, Sirvent, JJ, Gatell, JM, Vidal, F
Publicada:
1 jun 2014
Resumen:
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.
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 chi(2) test and Pearson and Spearman correlation analyses were carried out for statistical analysis.
LBP rs2232582 T -> C polymorphism was significantly associated with HALS (PaEuroS=aEuroS0.01 and PaEuroS=aEuroS0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (PaEuroS=aEuroS0.009) and LBP (PaEuroS < aEuroS0.001) were significantly higher and sCD14 significantly lower (PaEuroS < aEuroS0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (PaEuroS < aEuroS0.001) and hepatitis C virus (PaEuroS=aEuroS0.038), LBP levels by HALS (PaEuroS < aEuroS0.001) and sCD14 levels by age (PaEuroS=aEuroS0.008), current HIV-1 viral load (PaEuroS=aEuroS0.001) and protease inhibitor use (PaEuroS=aEuroS0.018).
HALS is associated with LBP polymorphism and with higher bacterial translocation.
Filiaciones:
Vilades, C:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, E-43007 Tarragona, Spain
Escote, X:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, E-43007 Tarragona, Spain
Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Asociadas CIBER, Tarragona, Spain
Lopez-Dupla, M:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, E-43007 Tarragona, Spain
Martinez, E:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Domingo, P:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Asensi, V:
Univ Oviedo, Hosp Gen Asturias, Oviedo, Spain
Leal, M:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio,Inst Biomed Sevilla IB, Lab Inmunovirol,Unidad Gest Clin Enfermedades Inf, Seville, Spain
Peraire, J:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, E-43007 Tarragona, Spain
Inza, MI:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, E-43007 Tarragona, Spain
Arnedo, M:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Gutierrez, M:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Valle-Garay, E:
Univ Oviedo, Hosp Gen Asturias, Oviedo, Spain
Ferrando-Martinez, S:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio,Inst Biomed Sevilla IB, Lab Inmunovirol,Unidad Gest Clin Enfermedades Inf, Seville, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Inst Invest Sanitaria Gregorio Maranon, Lab Inmunobiol Mol, Hosp Gen Univ Gregorio Maranon, Madrid, Spain
Olona, M:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, E-43007 Tarragona, Spain
Alba, V:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, E-43007 Tarragona, Spain
Sirvent, JJ:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, E-43007 Tarragona, Spain
Gatell, JM:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Vidal, F:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan XXIII, IISPV, E-43007 Tarragona, Spain
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