Background: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART) have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR) and their ligands class I human leukocyte antigen (HLA), could influence immunological response to cART. Methods: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4 + T-cell count <200/mm 3) and full responders (FR, N = 104, CD4 + T-cell count >350/mm 3). Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. Results: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005). The functional compound genotype HLA-C1 +/KIR2DL3 +, even at multivariable analysis, when adjusted for nadir CD4 + T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals) 0.34 (0.13-0.88), P = 0.03. Conclusions: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy. © 2011 Soria et al.

Soria, A., Guerini, F., Bandera, A., Bolognesi, E., Uglietti, A., Fusco, C., et al. (2011). KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy. PLOS ONE, 6(11), e27349 [10.1371/journal.pone.0027349].

KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy

SORIA, ALESSANDRO
;
BANDERA, ALESSANDRA;GORI, ANDREA
Ultimo
2011

Abstract

Background: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART) have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR) and their ligands class I human leukocyte antigen (HLA), could influence immunological response to cART. Methods: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4 + T-cell count <200/mm 3) and full responders (FR, N = 104, CD4 + T-cell count >350/mm 3). Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. Results: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005). The functional compound genotype HLA-C1 +/KIR2DL3 +, even at multivariable analysis, when adjusted for nadir CD4 + T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals) 0.34 (0.13-0.88), P = 0.03. Conclusions: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy. © 2011 Soria et al.
Articolo in rivista - Articolo scientifico
Scientifica
Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Cohort Studies; Female; Genotype; HIV Infections; HLA Antigens; Humans; Male; Middle Aged; Viral Load; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all)
English
Soria, A., Guerini, F., Bandera, A., Bolognesi, E., Uglietti, A., Fusco, C., et al. (2011). KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy. PLOS ONE, 6(11), e27349 [10.1371/journal.pone.0027349].
Soria, A; Guerini, F; Bandera, A; Bolognesi, E; Uglietti, A; Fusco, C; Zucchi, P; Maserati, R; Rizzardini, G; Clerici, M; Gori, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/62847
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