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Emergence of exhausted B cells in asymptomatic HIV-1-infected patients naïve for HAART is related to reduced immune surveillance.

Fogli M, Torti C, Malacarne F, Fiorentini S, Albani M, Izzo I, Giagulli C, Maggi F, Carosi G, Caruso A - Clin. Dev. Immunol. (2012)

Bottom Line: B cells alteration was related to an increase in Torque teno virus (TTV) load, used as surrogate marker of immune function.Successfully HAART-treated patients showed normalization of B cell subpopulations frequency and TTV load.These results provide new insights on B cell in HIV-1 infection and show that development of B cell abnormalities precedes CD4⁺ T cell decline.

View Article: PubMed Central - PubMed

Affiliation: Section of Microbiology, Department of Experimental and Applied Medicine, University of Brescia, Spedali Civili Square, 25123 Brescia, Italy.

ABSTRACT
Alterations of B cell subpopulations have been described up to date as characterizing advanced stage of HIV-1 infection. However, whether such defects are relevant in subjects with a preserved number of CD4⁺ T cells (>350 cells/μL) is unclear. In a cross-sectional study, we investigated if signs of B cells exhaustion and impaired viral immune surveillance are present in a cohort of 43 asymptomatic HIV-1-infected patients with preserved CD4⁺ T cell counts (>350 cells/μL) and highly active antiretroviral therapy (HAART) untreated. A dramatic expansion of exhausted tissue-like memory B cells (CD10⁻CD21(low)CD27⁻) was observed. B cells alteration was related to an increase in Torque teno virus (TTV) load, used as surrogate marker of immune function. Successfully HAART-treated patients showed normalization of B cell subpopulations frequency and TTV load. These results provide new insights on B cell in HIV-1 infection and show that development of B cell abnormalities precedes CD4⁺ T cell decline.

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Related in: MedlinePlus

Effect of HAART in B cell subsets distribution in HIV-1-infected patients. Comparative analysis of CD21 and CD27 expression on B cells from HIV-1-uninfected individuals, asymptomatic HIV-1-infected patients, and HAART-treated patients. Profiles of expression of CD21 and CD27 are shown for one representative of each groups (lower panel). Cells were gated according to the lymphocytes forward and side scatter pattern and the CD19+ cells (upper panel).
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fig5: Effect of HAART in B cell subsets distribution in HIV-1-infected patients. Comparative analysis of CD21 and CD27 expression on B cells from HIV-1-uninfected individuals, asymptomatic HIV-1-infected patients, and HAART-treated patients. Profiles of expression of CD21 and CD27 are shown for one representative of each groups (lower panel). Cells were gated according to the lymphocytes forward and side scatter pattern and the CD19+ cells (upper panel).

Mentions: We then investigated the effect of HAART on the B cell compartment of a cohort of HIV-1-infected individuals who experienced low levels of CD4+ T cell counts during the course of infection (median nadir: 183 cell/μL), and maintained undetectable HIV-1 viral load for the last 12 months of therapy. At the time of our study, all patients belonging to this cohort displayed CD4+ T cell counts higher than asymptomatic therapy-naïve HIV-1-infected patients (median 682 cells/μL versus 510 cell/μL, P < 0.0001). The absolute number of B cells was significantly higher in HAART-treated patients as compared to both asymptomatic HIV-1-infected HAART-naïve patients and healthy individuals (median: 233 cell/μL versus 129.5 cell/μL, P < 0.005, and versus 143 cell/μL, P < 0.01, resp.) (Table 3). In the cohort of HAART-treated patients we observed no presence of uncommon B cell populations with percentages of CD21lowCD27− and of CD21lowCD27+ B cells superimposable to those of healthy individuals (Figure 5). At the same time, the percentage of CD21highCD27− B cell subpopulation was higher in HAART-treated than asymptomatic HIV-1-infected cohort patients (P < 0.0005), and the IL-7 levels of treated-patients were superimposable to those of healthy donors. Finally, a successful immunological surveillance was observed in HAART-treated patients as they displayed a TTV plasma viremia within ranges commonly observed in healthy subjects (median: 4.1 versus 4.6 log⁡ DNA copies/mL).


Emergence of exhausted B cells in asymptomatic HIV-1-infected patients naïve for HAART is related to reduced immune surveillance.

Fogli M, Torti C, Malacarne F, Fiorentini S, Albani M, Izzo I, Giagulli C, Maggi F, Carosi G, Caruso A - Clin. Dev. Immunol. (2012)

Effect of HAART in B cell subsets distribution in HIV-1-infected patients. Comparative analysis of CD21 and CD27 expression on B cells from HIV-1-uninfected individuals, asymptomatic HIV-1-infected patients, and HAART-treated patients. Profiles of expression of CD21 and CD27 are shown for one representative of each groups (lower panel). Cells were gated according to the lymphocytes forward and side scatter pattern and the CD19+ cells (upper panel).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303688&req=5

fig5: Effect of HAART in B cell subsets distribution in HIV-1-infected patients. Comparative analysis of CD21 and CD27 expression on B cells from HIV-1-uninfected individuals, asymptomatic HIV-1-infected patients, and HAART-treated patients. Profiles of expression of CD21 and CD27 are shown for one representative of each groups (lower panel). Cells were gated according to the lymphocytes forward and side scatter pattern and the CD19+ cells (upper panel).
Mentions: We then investigated the effect of HAART on the B cell compartment of a cohort of HIV-1-infected individuals who experienced low levels of CD4+ T cell counts during the course of infection (median nadir: 183 cell/μL), and maintained undetectable HIV-1 viral load for the last 12 months of therapy. At the time of our study, all patients belonging to this cohort displayed CD4+ T cell counts higher than asymptomatic therapy-naïve HIV-1-infected patients (median 682 cells/μL versus 510 cell/μL, P < 0.0001). The absolute number of B cells was significantly higher in HAART-treated patients as compared to both asymptomatic HIV-1-infected HAART-naïve patients and healthy individuals (median: 233 cell/μL versus 129.5 cell/μL, P < 0.005, and versus 143 cell/μL, P < 0.01, resp.) (Table 3). In the cohort of HAART-treated patients we observed no presence of uncommon B cell populations with percentages of CD21lowCD27− and of CD21lowCD27+ B cells superimposable to those of healthy individuals (Figure 5). At the same time, the percentage of CD21highCD27− B cell subpopulation was higher in HAART-treated than asymptomatic HIV-1-infected cohort patients (P < 0.0005), and the IL-7 levels of treated-patients were superimposable to those of healthy donors. Finally, a successful immunological surveillance was observed in HAART-treated patients as they displayed a TTV plasma viremia within ranges commonly observed in healthy subjects (median: 4.1 versus 4.6 log⁡ DNA copies/mL).

Bottom Line: B cells alteration was related to an increase in Torque teno virus (TTV) load, used as surrogate marker of immune function.Successfully HAART-treated patients showed normalization of B cell subpopulations frequency and TTV load.These results provide new insights on B cell in HIV-1 infection and show that development of B cell abnormalities precedes CD4⁺ T cell decline.

View Article: PubMed Central - PubMed

Affiliation: Section of Microbiology, Department of Experimental and Applied Medicine, University of Brescia, Spedali Civili Square, 25123 Brescia, Italy.

ABSTRACT
Alterations of B cell subpopulations have been described up to date as characterizing advanced stage of HIV-1 infection. However, whether such defects are relevant in subjects with a preserved number of CD4⁺ T cells (>350 cells/μL) is unclear. In a cross-sectional study, we investigated if signs of B cells exhaustion and impaired viral immune surveillance are present in a cohort of 43 asymptomatic HIV-1-infected patients with preserved CD4⁺ T cell counts (>350 cells/μL) and highly active antiretroviral therapy (HAART) untreated. A dramatic expansion of exhausted tissue-like memory B cells (CD10⁻CD21(low)CD27⁻) was observed. B cells alteration was related to an increase in Torque teno virus (TTV) load, used as surrogate marker of immune function. Successfully HAART-treated patients showed normalization of B cell subpopulations frequency and TTV load. These results provide new insights on B cell in HIV-1 infection and show that development of B cell abnormalities precedes CD4⁺ T cell decline.

Show MeSH
Related in: MedlinePlus