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. 2016 Jul 22:16:344.
doi: 10.1186/s12879-016-1647-3.

Association between different anti-Tat antibody isotypes and HIV disease progression: data from an African cohort

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Association between different anti-Tat antibody isotypes and HIV disease progression: data from an African cohort

Francesco Nicoli et al. BMC Infect Dis. .

Abstract

Background: The presence of IgG and IgM against Tat, an HIV protein important for viral replication and immune dysfunction, is associated with slow disease progression in clade B HIV-infected individuals. However, although Tat activities strictly depend on the viral clade, our knowledge about the importance of anti-Tat antibodies in non-clade B HIV infection is poor. The objective of this study was to investigate the association of different anti-Tat antibody isotypes with disease progression in non-clade B HIV-infected subjects and to study the relationship between anti-Tat humoral responses and immunological abnormalities.

Methods: Anti-clade B and -clade C Tat IgG, IgM and IgA titers were assessed in serum samples from 96 cART-naïve subjects with chronic HIV infection from Mbeya, Tanzania, and associated with CD4(+) T cell count, plasma viremia and CD4(+) and CD8(+) T cell phenotypes.

Results: Anti-Tat IgM were preferentially detected in chronic HIV-infected subjects with low T cell activation (p-value = 0.03) and correlated with higher CD4(+) T cell counts and lower viral loads irrespective of the duration of infection (p-value = 0.019 and p-value = 0.037 respectively). Conversely, anti-Tat IgA were preferentially detected in individuals with low CD4(+) T cell counts and high viral load (p-value = 0.02 and p-value < 0.001 respectively). The simultaneous presence of anti-Tat IgG and IgM protected from fast CD4(+) T cell decline (p-value < 0.01) and accumulation of CD38(+)HLADR(+)CD8(+) T cells (p- value = 0.029).

Conclusions: Anti-Tat IgG alone are not protective in non-clade B infected subjects, unless concomitant with IgM, suggesting a protective role of persistent anti-Tat IgM irrespective of the infecting clade.

Keywords: Antibodies; Clade B HIV; Clade C HIV; Diseases progression; Immune activation; Tat.

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Figures

Fig. 1
Fig. 1
Prevalence and cross-clade reactivity of anti-Tat antibodies. CART-naïve, chronically HIV-infected individuals (n = 96) were tested for the presence of anti-Tat antibodies by ELISA. a Percentage of subjects with anti-clade C Tat IgG, IgA or IgM or anti-clade C Tat negative. b Number of anti-clade C Tat positive individuals able to recognize clade B Tat. c Number of subjects able to recognize clade B but not clade C Tat. d Heatmap showing, for single donors, positivity (black) or negativity (grey) toward clade C or clade B Tat for each isotype after unsupervised clustering. e Venn diagram analyses of the number of subjects recognizing clade B and/or C Tat stratified by the antibody isotype displayed
Fig. 2
Fig. 2
Association of anti-Tat antibody isotypes with CD4+ T cell count and viral load. Subjects were stratified according to the type and number of the anti-Tat antibody isotypes detected. Subgroups were compared for (a) CD4+ T cell count or (b) Log10 plasma viral load. Lines represent the median value. Statistical comparisons were made using the Mann-Whitney test. c Subjects were plotted according to both CD4+ T cell count and Log10 plasma viral load. Empty circles represent subjects with anti-Tat IgG and/or IgM but not IgA, grey squares represent subjects with anti-Tat IgA, black triangles represent anti-Tat antibody negative subjects
Fig. 3
Fig. 3
Association of anti-Tat antibody isotypes with immunological abnormalities. a Subjects were stratified according to the activation burden. Subjects in panels (b-d) were stratified according to the type and number of anti-Tat antibody isotypes. b Subgroups were compared for CD4:CD8 ratio. c Subgroups were compared for percentages of CD38+ HLA-DR+ on CD8+ (left panel) and CD4+ T cells (right panel). d Subgroups were compared for CD8+ (left panel) and CD4+ (right panel) T cell subpopulations. Solid lines in panels (b-c) represent the median value while bars in panel (d) represent the median values with interquartile range. Statistical comparisons were made using Fisher’s exact probability test (a) and Mann-Whitney test (b-d)
Fig. 4
Fig. 4
Association of different anti-Tat antibody isotypes with disease progression. a Subjects were stratified according to the tertiles of CD4+ T cell decline. Black bars represent subjects with any anti-Tat antibody isotype (top panel) or with anti-Tat IgG and IgM (bottom panel). Statistical comparisons were made using Fisher’s exact probability test. b Subjects were stratified according to the type and number of anti-Tat antibody isotypes. Subgroups were compared for absolute differences of CD38+HLA-DR+CD8+ T and CD38+HLA-DR+CD4+ T cell percentages. Absolute differences were obtained by subtracting baseline values from values collected at 1 year follow up visit. Data are presented as Box-and-Whisker Plots. Statistical significance of absolute difference was calculated using Wilcoxon signed rank test; p-values < 0.05 indicates that differences are significantly different from 0

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