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Research Paper

Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy

, , , , , , & show all
Pages 1995-2002 | Received 15 Dec 2017, Accepted 08 Apr 2018, Published online: 17 May 2018

Figures & data

Table 1. Host genetic variants' distribution according to immunization response and vaccine product quality. 24 polymorphisms in 16 genes related with HIV-1 restriction and/or DC-based HIV immunotherapy response were genotyped in 19 HIV+ patients submitted to a phase I/II clinical trial of DC-based HIV immunotherapy. Multivariate analysis of polymorphisms' distribution was performed according to “immunization response” (ΔPVL, ΔT CD4+, ΔT CD8+), “dendritic cells quality” (DC yield, CD83+ cells, IL-10 production), “ability of DC in inducing a T CD4+ or CD8+ cell response” (IL-2+, IFN-γ+, TNF+ and MIP-1ß+ cells, and cell proliferation after 24 or 96 hours of DC/lymphocytes co-culture). Sex, age and time from diagnosis were included in the analysis as confounder variables. Herein only main results are presented (padj ≤ 0.05). Statistical significant p-values, according to Bonferroni correction (padj ≤ 0.002), are indicated in bold characters Gene name, polymorphism identification number (ID), minor allele, genotypes and their distribution (n), variables' mean value and standard error (mean ± SE), as well as p-values adjusted for sex, age and time from diagnosis (padj). ΔPVL: variation in plasma viral load after the immunization; ΔT CD4+: variation in peripheral blood T CD4+ cells count after the immunization; ΔT CD8+: variation in peripheral blood T CD8+ cells count after the immunization. PVL is expressed in log (RNA copies/µL). T cells count is expressed as number of cells/µL. Flow cytometry data are expressed as percentage of positive cells (%) or median fluorescence intensity (MFI) for the used markers. Cytokines production by DC is expressed as concentration in culture supernatant (pg/mL). T lymphocytes proliferation is expressed as percentage (%) of CSFE cell staining dye.

Table 2. PBMC gene expression profile according to immunization response and vaccine product quality. The expression of 86 genes related with HIV progression/AIDS or immunization response was evaluated in peripheral blood mononuclear cells (PBMC) isolated from 19 HIV+ patients before (t0) and after (t1) immunization with autologous HIV-stimulated DC (phase I/II trial of DC-based immunotherapy). The modulation of gene expression was calculated as Fold Change/FC (2−ΔΔCt > 1) or Fold Regulation/FR (2−ΔΔCt < 1) according to Schmittgen and Livak,Citation25 and genes with a FC > 1.2 or FR < −1.2 were considered differentially expressed after the treatment (differential expressed genes, DEGs). Non-parametric Spearman test of correlation was performed between DEGs and “immunization response” (ΔPVL, ΔT CD4+, ΔT CD8+), “dendritic cells quality” (DC yield, CD83+ cells, IL-10 production), or “ability of DC in inducing a T CD4+ or CD8+ cell response” (IL-2+, IFN-γ+, TNF+ and MIP-1ß+ cells, and cell proliferation after 24 or 96 hours of DC/lymphocytes co-culture). Herein only main results are presented (r2 ≥ 0.95 and p ≤ 0.05). Variable name, gene name, FC or FR mean value and standard error (mean ± SE), as well as Spearman correlation parameters (r2 and p-value) were reported. ΔPVL: variation in plasma viral load after the immunization; ΔT CD4+: variation in peripheral blood T CD4+ cells count after the immunization; ΔT CD8+: variation in peripheral blood T CD8+ cells count after the immunization. PVL is expressed in log (RNA copies/µL). T cells count is expressed as number of cells/µL. Flow cytometry data are expressed as percentage of positive cells (%) or median fluorescence intensity (MFI) for the used markers. Cytokines production by DC is expressed as concentration in culture supernatant (pg/mL). T lymphocytes proliferation is expressed as percentage (%) of CSFE cell staining dye.

Table 3. Main characteristics of immunized HIV+ individuals.

Supplemental material

KHVI_A_1463942_Supplemental.zip

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