All independent predictor candidates were transformed into variab

All independent predictor candidates were transformed into variable-dependent tertile numbers, which were arranged in such a manner that a high tertile number was considered unfavourable

in terms of CD4 loss. In univariate analysis, the E/G and E/G neg ratios were not only the strongest predictors of current CD4 change rate, but in this limited cohort also the only significant predictors. For example, the odds ratio for rapid CD4 loss was 8·0 between patients within the lowest and the highest tertile of E/G ratios (i.e. 4·0 × 2 learn more tertiles, Table 4). CD38 expression and Gag-specific CD8+ responses per se were also predictive for high relative and guideline-restricted CD4 loss rates, in contrast to HIV-RNA and β2-microglobulin (Table 4). No significant results in multivariate binary regression model were found. Clinical evaluation of asymptomatic and untreated HIV-infected patients should be based upon prognostic markers with sufficient statistical power for individual counselling. HIV-RNA levels, for Dabrafenib datasheet example, correlates clearly with clinical progression in large cohorts but predicts progression poorly at

the individual level [11–13]. Thus, optimal markers of progression should provide significant information even in small cohorts. This explorative study investigated new parameters for HIV-specific immunity in the search for optimal prognostic markers. The main goals of this study were to investigate prognostic significance of HIV-specific T cell responses to Gag, Env and Nef and of PD-1 on such HIV-specific cells. Specific clones were detected through transient expression of CD107a and CD154. These data were compared to quantitative measurements of CD38 on CD8+ and CD8+CD38+PD-1+ GNA12 T cells and correlated subsequently to progression, which in asymptomatic patients may be best described by CD4+ T cell loss rates. Furthermore, fresh blood samples as opposed to thawed PBMC were analysed due to the decay of CD38 on thawed PBMC [14], possible preferential loss of CD8+ T cells [38] and limited robustness of the CD107a assay.

Two mainly affirmative observations were made: a predominance of Gag-restricted CD8+ T cell responses and their relation to prognosis [20] and a high expression of PD-1 molecules on such HIV-specific CD8+ T cells [30]. In addition, this study provided new data showing up-regulated PD-1 on HIV-specific CD4+ T cells, but differently than on the CD8+ subset as well as a lower expression of PD-1 on Env-specific CD8+ T cells compared with Gag-specific cells (Fig. 1a). Subsequently, the data on relative and absolute abundance of HIV-specific responses, including the estimates of PD-1, were related to CD4 loss rates. The total number of Gag-specific CD8+ cells were correlated even stronger with CD4 loss rates and immune activation than the conventional frequency estimates (Table 3) supporting the relevance of taking the CD8+ T cell count into consideration.

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