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

Alessandro Soria, Franca Rosa Guerini, Alessandra Bandera, Elisabetta Bolognesi, Alessia Uglietti, Caterina Fusco, Patrizia Zucchi, Renato Maserati, Giuliano Rizzardini, Mario Clerici, Andrea Gori

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 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.

Original languageEnglish
Article numbere27349
JournalPLoS One
Volume6
Issue number11
DOIs
Publication statusPublished - Nov 3 2011

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KIR Receptors
International Normalized Ratio
T-cells
HLA Antigens
immunoglobulins
CD4 Lymphocyte Count
Genotype
HIV
Recovery
therapeutics
receptors
T-lymphocytes
genotype
T-Lymphocytes
Gene encoding
Polymerase chain reaction
Polymorphism
Therapeutics
viral load
Viral Load

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy. / Soria, Alessandro; Guerini, Franca Rosa; Bandera, Alessandra; Bolognesi, Elisabetta; Uglietti, Alessia; Fusco, Caterina; Zucchi, Patrizia; Maserati, Renato; Rizzardini, Giuliano; Clerici, Mario; Gori, Andrea.

In: PLoS One, Vol. 6, No. 11, e27349, 03.11.2011.

Research output: Contribution to journalArticle

Soria, Alessandro ; Guerini, Franca Rosa ; Bandera, Alessandra ; Bolognesi, Elisabetta ; Uglietti, Alessia ; Fusco, Caterina ; Zucchi, Patrizia ; Maserati, Renato ; Rizzardini, Giuliano ; Clerici, Mario ; Gori, Andrea. / KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy. In: PLoS One. 2011 ; Vol. 6, No. 11.
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AU - Bolognesi, Elisabetta

AU - Uglietti, Alessia

AU - Fusco, Caterina

AU - Zucchi, Patrizia

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N2 - 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 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.

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