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Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

Pogliaghi M, Ripa M, Pensieroso S, Tolazzi M, Chiappetta S, Nozza S, Lazzarin A, Tambussi G, Scarlatti G - PLoS ONE (2015)

Bottom Line: Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets.In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART.After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

View Article: PubMed Central - PubMed

Affiliation: Università Vita-Salute San Raffaele, Milan, Italy; Department of Infectious and Tropical Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.

ABSTRACT

Introduction: During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART).

Materials and methods: To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation.

Results: Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups.

Conclusions: In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

No MeSH data available.


Related in: MedlinePlus

Immunoglobulin expression of B-cell subsets.Indicated are frequencies of Ig-expression on RM, AM and TLM B-cells in PHI, CHI and CS. Ig-expressing B-cells are defined as IgM-only “IgM+” (IgM+IgD-), IgD-expressing “IgD+” (IgM-IgD+), Marginal-Zone like “MZ” (IgM+IgD+) and Switched “SW” (IgM-IgD-) B-cells. The column plots to the right represent the median frequencies of Ig-expression in the B-cell subsets, the tables to the left indicate p-values of comparisons (* = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, ns = not significant, Mann-Whitney test). A. Frequencies of PHI and CHI individuals at BL in comparison to CS. B. Frequencies of PHI and CHI individuals at week 4 (W4) in comparison to CS. C. Frequencies of PHI and CHI individuals at week 48 (W48) in comparison to CS.
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pone.0140435.g003: Immunoglobulin expression of B-cell subsets.Indicated are frequencies of Ig-expression on RM, AM and TLM B-cells in PHI, CHI and CS. Ig-expressing B-cells are defined as IgM-only “IgM+” (IgM+IgD-), IgD-expressing “IgD+” (IgM-IgD+), Marginal-Zone like “MZ” (IgM+IgD+) and Switched “SW” (IgM-IgD-) B-cells. The column plots to the right represent the median frequencies of Ig-expression in the B-cell subsets, the tables to the left indicate p-values of comparisons (* = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, ns = not significant, Mann-Whitney test). A. Frequencies of PHI and CHI individuals at BL in comparison to CS. B. Frequencies of PHI and CHI individuals at week 4 (W4) in comparison to CS. C. Frequencies of PHI and CHI individuals at week 48 (W48) in comparison to CS.

Mentions: We first determined the frequencies of these phenotypes in healthy controls (Fig 3). SW cells, as expected, were the major compartment among all Memory B-cell subsets, while MZL were the second most represented population. IgM+ were the third compartment, except for TLM, where they were the least represented subset. Finally, IgD+ compartment was the least represented among AM and RM B-cells.


Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

Pogliaghi M, Ripa M, Pensieroso S, Tolazzi M, Chiappetta S, Nozza S, Lazzarin A, Tambussi G, Scarlatti G - PLoS ONE (2015)

Immunoglobulin expression of B-cell subsets.Indicated are frequencies of Ig-expression on RM, AM and TLM B-cells in PHI, CHI and CS. Ig-expressing B-cells are defined as IgM-only “IgM+” (IgM+IgD-), IgD-expressing “IgD+” (IgM-IgD+), Marginal-Zone like “MZ” (IgM+IgD+) and Switched “SW” (IgM-IgD-) B-cells. The column plots to the right represent the median frequencies of Ig-expression in the B-cell subsets, the tables to the left indicate p-values of comparisons (* = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, ns = not significant, Mann-Whitney test). A. Frequencies of PHI and CHI individuals at BL in comparison to CS. B. Frequencies of PHI and CHI individuals at week 4 (W4) in comparison to CS. C. Frequencies of PHI and CHI individuals at week 48 (W48) in comparison to CS.
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Related In: Results  -  Collection

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pone.0140435.g003: Immunoglobulin expression of B-cell subsets.Indicated are frequencies of Ig-expression on RM, AM and TLM B-cells in PHI, CHI and CS. Ig-expressing B-cells are defined as IgM-only “IgM+” (IgM+IgD-), IgD-expressing “IgD+” (IgM-IgD+), Marginal-Zone like “MZ” (IgM+IgD+) and Switched “SW” (IgM-IgD-) B-cells. The column plots to the right represent the median frequencies of Ig-expression in the B-cell subsets, the tables to the left indicate p-values of comparisons (* = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, ns = not significant, Mann-Whitney test). A. Frequencies of PHI and CHI individuals at BL in comparison to CS. B. Frequencies of PHI and CHI individuals at week 4 (W4) in comparison to CS. C. Frequencies of PHI and CHI individuals at week 48 (W48) in comparison to CS.
Mentions: We first determined the frequencies of these phenotypes in healthy controls (Fig 3). SW cells, as expected, were the major compartment among all Memory B-cell subsets, while MZL were the second most represented population. IgM+ were the third compartment, except for TLM, where they were the least represented subset. Finally, IgD+ compartment was the least represented among AM and RM B-cells.

Bottom Line: Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets.In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART.After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

View Article: PubMed Central - PubMed

Affiliation: Università Vita-Salute San Raffaele, Milan, Italy; Department of Infectious and Tropical Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.

ABSTRACT

Introduction: During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART).

Materials and methods: To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation.

Results: Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups.

Conclusions: In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

No MeSH data available.


Related in: MedlinePlus