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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

Evolution in Immunoglobulin expression of B-cell subsets in study groups vs CS.Each panel represents changes over time of different Ig-subsets in Resting Memory, Activated Memory, and Tissue-like Memory B-cell of PHI and CHI individuals: A. Switched cells; B. Marginal zone-like cells; C. IgM+ cells; D. IgD+ cells. Dotted horizontal line represents the mean of the CS individuals for a given cell population. P values are * = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, obtained with Two-sample paired sign test.
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pone.0140435.g004: Evolution in Immunoglobulin expression of B-cell subsets in study groups vs CS.Each panel represents changes over time of different Ig-subsets in Resting Memory, Activated Memory, and Tissue-like Memory B-cell of PHI and CHI individuals: A. Switched cells; B. Marginal zone-like cells; C. IgM+ cells; D. IgD+ cells. Dotted horizontal line represents the mean of the CS individuals for a given cell population. P values are * = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, obtained with Two-sample paired sign test.

Mentions: After 4 weeks of cART, in PHI SW cells significantly dropped in AM and TLM B-cells and did not change in RM cells (Fig 4, panel A). Interestingly, SW cells in PHI patients reached levels comparable to those observed in CHI individuals at BL (Fig 3, panel A and B). Conversely, in CHI all SW Memory subsets significantly raised (Fig 4, panel A), although not reaching frequencies seen in healthy controls. At week 48 of cART, SW cells increased in most of memory B-cell subsets of both PHI and CHI (Fig 4, panel A), finally reaching levels comparable to healthy controls for all memory subsets (Fig 3, panel C).


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)

Evolution in Immunoglobulin expression of B-cell subsets in study groups vs CS.Each panel represents changes over time of different Ig-subsets in Resting Memory, Activated Memory, and Tissue-like Memory B-cell of PHI and CHI individuals: A. Switched cells; B. Marginal zone-like cells; C. IgM+ cells; D. IgD+ cells. Dotted horizontal line represents the mean of the CS individuals for a given cell population. P values are * = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, obtained with Two-sample paired sign test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608708&req=5

pone.0140435.g004: Evolution in Immunoglobulin expression of B-cell subsets in study groups vs CS.Each panel represents changes over time of different Ig-subsets in Resting Memory, Activated Memory, and Tissue-like Memory B-cell of PHI and CHI individuals: A. Switched cells; B. Marginal zone-like cells; C. IgM+ cells; D. IgD+ cells. Dotted horizontal line represents the mean of the CS individuals for a given cell population. P values are * = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, obtained with Two-sample paired sign test.
Mentions: After 4 weeks of cART, in PHI SW cells significantly dropped in AM and TLM B-cells and did not change in RM cells (Fig 4, panel A). Interestingly, SW cells in PHI patients reached levels comparable to those observed in CHI individuals at BL (Fig 3, panel A and B). Conversely, in CHI all SW Memory subsets significantly raised (Fig 4, panel A), although not reaching frequencies seen in healthy controls. At week 48 of cART, SW cells increased in most of memory B-cell subsets of both PHI and CHI (Fig 4, panel A), finally reaching levels comparable to healthy controls for all memory subsets (Fig 3, panel C).

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