IFNAR-1 mRNA levels before and after treatment with IFN-alpha in PBMC from naive HCV-infected patients.

<p>Total cellular RNA was extracted and reverse-transcribed from PBMC of naive HCV-infected patients carrying different IL-28B rs12979869 genotypes CC, TT and CT before (<b>Panel A</b>) and after 3 h of exposure to 10³ IU/ml IFN-alpha (<b>Panel B</b>), then mRNA levels for IFNAR-1 were measured. Results are expressed as ratio to beta-actin (median, IQR).</p

Characteristics of 32 treatment naive HCV-infected patients included in the study.

<p>Characteristics of 32 treatment naive HCV-infected patients included in the study.</p

Levels of IFNAR-1 mRNA in PBMC from the HCV-infected naïve subjects after 3h of exposure to 10³ IU/ml IFN-alpha2b <i>in vitro</i>, according to their <i>IFNL3</i> and <i>IFNL4</i> genotype combinations.

<p>Group 1: <i>IFNL3</i> CC and <i>IFNL4</i> TT/TT (<i>IFNL3</i> favourable, <i>IFNL4</i> favourable) n = 6; Group 2: <i>IFNL3</i> CT or TT and <i>IFNL4</i> TT/TT (<i>IFNL3</i> unfavourable and <i>IFNL4</i> favourable) n = 11; Group 3: <i>IFNL3</i> CT or TT and <i>IFNL4</i> TT/ΔG or ΔG/ΔG (<i>IFNL3</i> and <i>IFNL4</i> unfavourable) n = 11. The results are expressed as ratio to beta-actin, after subtraction of values from unexposed cultures (median, IQR).</p

Levels of IFNAR-1 mRNA in PBMC from HCV-infected naїve subjects carrying <i>IFNL4</i> ss469415590 TT/TT genotype vs patients carrying the ΔG allele.

<p>Results are expressed as ratio to beta-actin. The horizontal bar indicates median.</p

Time dependent induction of IFNAR-1 mRNA levels following treatment with IFN-lambda in PBMC from healthy donors.

<p>PBMC were exposed to control medium (▪) 10 ng/mL (▪) and 100 ng/mL (□) of IFN-lambda, then mRNA levels for IFNAR-1 were measured at different time points (0, 3, 6, 12 and 24 h). Results are expressed as ratio to beta-actin. Results from one representative experiment performed on PBMC from two healthy donors with IL-28B rs12979860 CC (<b>Panel A</b>) and TT (<b>Panel B</b>) genotype are shown.</p

Levels of IFNAR-1 mRNA in PBMC from the HCV-infected naïve subjects grouped according to their <i>IFNL3</i> and <i>IFNL4</i> genotype combinations.

<p>Panel A. Group 1: <i>IFNL3</i> CC and <i>IFNL4</i> TT/TT (<i>IFNL3</i> favourable, <i>IFNL4</i> favourable), n = 8; Group 2: <i>IFNL3</i> CT or TT and <i>IFNL4</i> TT/TT (<i>IFNL3</i> unfavourable and <i>IFNL4</i> favourable) n = 10; Group 3: <i>IFNL3</i> CT or TT and <i>IFNL4</i> TT/ΔG or ΔG/ΔG (<i>IFNL3</i> and <i>IFNL4</i> unfavourable) n = 14. The results are expressed as ratio to beta-actin (median, IQR). Levels of IP10 mRNA in PBMC from the various groups after 3h of exposure to 10³ IU/ml IFN-alpha2b <i>in vitro</i>, according to their <i>IFNL3</i> and <i>IFNL4</i> genotype combinations. Panel B. Group 1: <i>IFNL3</i> CC and <i>IFNL4</i> TT/TT (<i>IFNL3</i> favourable, <i>IFNL4</i> favourable) n = 6; Group 2: <i>IFNL3</i> CT or TT and <i>IFNL4</i> TT/TT (IFNL3 unfavourable and <i>IFNL4</i> favourable) n = 11; Group 3: <i>IFNL3</i> CT or TT and <i>IFNL4</i> TT/ΔG or ΔG/ΔG (<i>IFNL3</i> and <i>IFNL4</i> unfavourable) n = 11. The results are expressed as ratio to beta-actin, after subtraction of values from unexposed cultures (median, IQR). The range of IP10 mRNA levels in unexposed PBMC cultures was 0,375 to 0,967.</p

Cellular immune response to different influenza A virus strains.

<p>(A): The frequency of T-cell response specific for A/H3N2/Min/11/10, A/H3N2/Ind/08/11 and for A/H1N1/Cal/07/09 was evaluated by ELISpot assay in HD (n = 45, white bars) and HIV+ patients (n = 46 grey bars). Results are indicated as SCFs/10⁶ peripheral mononuclear cells (PBMCs). Statistical analysis was performed using non parametric Mann-Whitney assay. ** p<0.0001. (B): The correlation between T-cell response against A/H3N2/Min/11/10 and A/H3N2/Ind/08/11 is shown, with Pearson's r² and significance, as well as the calculated regression line. HD and HIV+ are reported as white and black circles, respectively.</p

Correlation between humoral immune response to H3N2v strains.

<p>(A): The correlation between HAI titers to A/H3N2/Min/11/10 and to A/H3N2/Ind/08/11 is shown in HD. Pearson's r² and significance, as well as the calculated regression line. (B): The correlation between HAI titers to A/H3N2/Min/11/10 and to A/H3N2/Ind/08/11 is shown in HIV+. Pearson's r² and significance, as well as the calculated regression line.</p

Association between age and cellular immune response to different influenza A virus strains.

<p>The potential and the shape of association between age and T-cell response against A/H3N2/Min/11/10, A/H3N2/Ind/08/11 and A/H1N1/Cal/07/09 is shown for HD (left panels) and HIV+ (right panels) was analyzed by linear regression model. Departure from linear trend was assessed by model based likelihood ratio test (LTR) to assess the model including age as polynomial predictor.</p

Frequency of HD and HIV+ presenting a T-cell response to different influenza A virus strains.

<p><b>* chi-square test:</b></p><p>**p = 0.0023.</p><p>Frequency of HD and HIV+ presenting a T-cell response to different influenza A virus strains.</p