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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

Viro-immunological follow-up of study groups.CD4+ T-cell count (cells/mm3) and plasma viremia (log copies/ml) for PHI and CHI patients are here represented. Left panels show medians with IQR of each parameter; right panels show median values of each time-point to highlight the trend over time. P values are * = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, obtained with Mann-Whitney test for left panels and with Two-sample paired sign test for right panels.
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pone.0140435.g001: Viro-immunological follow-up of study groups.CD4+ T-cell count (cells/mm3) and plasma viremia (log copies/ml) for PHI and CHI patients are here represented. Left panels show medians with IQR of each parameter; right panels show median values of each time-point to highlight the trend over time. P values are * = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, obtained with Mann-Whitney test for left panels and with Two-sample paired sign test for right panels.

Mentions: As expected, PHI had significantly higher plasma HIV-1-RNA load and CD4+ T-cell count at BL in comparison to CHI (Table 1 and Fig 1). Notably, alanine aminotransferase (ALT) were higher in PHI patients, probably due to the hepatic involvement during PHI (Table 1). cART was started for both PHI and CHI with regimens specific to each study protocol as described in Materials and Methods section. HIV-1-RNA load decreased by 4 weeks of treatment in both groups, but still remained higher in PHI compared to CHI (Fig 1). Virological suppression, defined as plasma HIV-1-RNA below 50 copies/ml, was obtained at 48 weeks in 18 out of 19 PHI and in all CHI. After cART initiation CD4+ T-cell count increased in the two groups through-out the whole follow-up reaching similar levels at 4 weeks, whereas at 48 weeks PHI had higher CD4+ T-cell counts than CHI (Fig 1). No differences in terms of CD4+ T-cell gain or in decrease of HIV-1-RNA load were observed between the different cART regimens applied (data not shown).


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)

Viro-immunological follow-up of study groups.CD4+ T-cell count (cells/mm3) and plasma viremia (log copies/ml) for PHI and CHI patients are here represented. Left panels show medians with IQR of each parameter; right panels show median values of each time-point to highlight the trend over time. P values are * = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, obtained with Mann-Whitney test for left panels and with Two-sample paired sign test for right panels.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140435.g001: Viro-immunological follow-up of study groups.CD4+ T-cell count (cells/mm3) and plasma viremia (log copies/ml) for PHI and CHI patients are here represented. Left panels show medians with IQR of each parameter; right panels show median values of each time-point to highlight the trend over time. P values are * = 0.01–0.05, ** = 0.001–0.01, *** = <0.001, obtained with Mann-Whitney test for left panels and with Two-sample paired sign test for right panels.
Mentions: As expected, PHI had significantly higher plasma HIV-1-RNA load and CD4+ T-cell count at BL in comparison to CHI (Table 1 and Fig 1). Notably, alanine aminotransferase (ALT) were higher in PHI patients, probably due to the hepatic involvement during PHI (Table 1). cART was started for both PHI and CHI with regimens specific to each study protocol as described in Materials and Methods section. HIV-1-RNA load decreased by 4 weeks of treatment in both groups, but still remained higher in PHI compared to CHI (Fig 1). Virological suppression, defined as plasma HIV-1-RNA below 50 copies/ml, was obtained at 48 weeks in 18 out of 19 PHI and in all CHI. After cART initiation CD4+ T-cell count increased in the two groups through-out the whole follow-up reaching similar levels at 4 weeks, whereas at 48 weeks PHI had higher CD4+ T-cell counts than CHI (Fig 1). No differences in terms of CD4+ T-cell gain or in decrease of HIV-1-RNA load were observed between the different cART regimens applied (data not shown).

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