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Delayed reconstitution of B cell immunity to pneumococcus in HIV-infected Malawian children on antiretroviral therapy.

Iwajomo OH, Moons P, Nkhata R, Mzinza D, Ogunniyi AD, Williams NA, Heyderman RS, Finn A - J. Infect. (2014)

Bottom Line: The proportions of mature naïve B cells (CD19(+) CD10(-) CD27(-) CD21(hi)) and resting memory B cells (CD19(+) CD27(+) CD21(hi)) increased and apoptosis-prone mature activated B cells (CD19(+) CD21(lo) CD10(-)) decreased markedly by 12 months.These data show that, in chronically HIV-infected children receiving ART, improvement in B-cell memory profiles and function is slower than CD4(+) T-cells.This supports early initiation of ART and informs research into optimal timing of immunization with pneumococcal vaccines.

View Article: PubMed Central - PubMed

Affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.

No MeSH data available.


Related in: MedlinePlus

Pneumococcal protein antigen specific IgG memory B cells increase after 12 months' antiretroviral therapy (ART) in HIV-infected Malawian children. Using an enzyme-linked immunospot (ELISPOT) assay, following the expansion of memory B cells with a cocktail of mitogens (standardized pansorbin cells, pokeweed mitogen extract and phosphothiolated CpG oligodeoxynucleotide 2006) for six days, (A) Choline binding protein A (CbpA), (B) Pneumococcal surface protein A (PspA), (C) Pneumolysin (Ply), and (D) Pneumococcal surface antigen A (PsaA) specific IgG antibody secreting cells (ASCs) were enumerated in HIV-infected children on ART. Memory B cell responses were expressed as numbers of antibody secreting cells (ASCs) per million cultured peripheral blood mononuclear cells (PBMCs) seeded on the ELISPOT well. Each dot represents an average of test wells performed in triplicate. Horizontal bars represent median values. The broken horizontal lines in A–C represent median values in HIV-uninfected controls recruited as part of separate contemporaneous study reported elsewhere.10 The interquartile range for these controls has been incorporated in the y-axis except the upper quartile band for CbpA specific memory B cells of 44.2 that was not incorporated owing to axis break. PsaA specific memory B cells were not measured in the HIV-uninfected cohort. Comparisons were made using Friedman's test to evaluate the effect of ART across all time points.
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fig3: Pneumococcal protein antigen specific IgG memory B cells increase after 12 months' antiretroviral therapy (ART) in HIV-infected Malawian children. Using an enzyme-linked immunospot (ELISPOT) assay, following the expansion of memory B cells with a cocktail of mitogens (standardized pansorbin cells, pokeweed mitogen extract and phosphothiolated CpG oligodeoxynucleotide 2006) for six days, (A) Choline binding protein A (CbpA), (B) Pneumococcal surface protein A (PspA), (C) Pneumolysin (Ply), and (D) Pneumococcal surface antigen A (PsaA) specific IgG antibody secreting cells (ASCs) were enumerated in HIV-infected children on ART. Memory B cell responses were expressed as numbers of antibody secreting cells (ASCs) per million cultured peripheral blood mononuclear cells (PBMCs) seeded on the ELISPOT well. Each dot represents an average of test wells performed in triplicate. Horizontal bars represent median values. The broken horizontal lines in A–C represent median values in HIV-uninfected controls recruited as part of separate contemporaneous study reported elsewhere.10 The interquartile range for these controls has been incorporated in the y-axis except the upper quartile band for CbpA specific memory B cells of 44.2 that was not incorporated owing to axis break. PsaA specific memory B cells were not measured in the HIV-uninfected cohort. Comparisons were made using Friedman's test to evaluate the effect of ART across all time points.

Mentions: In contrast to total B cell subsets, recovery in numbers of circulating memory B cells specific for four pneumococcal antigens (Choline binding protein A (CbpA), Pneumococcal surface protein A (PspA), Pneumolysin (Ply) and Pneumococcal surface antigen A (PsaA)) only became apparent during the latter part of the 12 month observation period (P = 0.007, P = 0.02, P = 0.02, P = 0.001 respectively (Fig. 3)). Median values approached those seen in uninfected controls by 12 months for two of the three antigens for which control data were available (Fig. 3).


Delayed reconstitution of B cell immunity to pneumococcus in HIV-infected Malawian children on antiretroviral therapy.

Iwajomo OH, Moons P, Nkhata R, Mzinza D, Ogunniyi AD, Williams NA, Heyderman RS, Finn A - J. Infect. (2014)

Pneumococcal protein antigen specific IgG memory B cells increase after 12 months' antiretroviral therapy (ART) in HIV-infected Malawian children. Using an enzyme-linked immunospot (ELISPOT) assay, following the expansion of memory B cells with a cocktail of mitogens (standardized pansorbin cells, pokeweed mitogen extract and phosphothiolated CpG oligodeoxynucleotide 2006) for six days, (A) Choline binding protein A (CbpA), (B) Pneumococcal surface protein A (PspA), (C) Pneumolysin (Ply), and (D) Pneumococcal surface antigen A (PsaA) specific IgG antibody secreting cells (ASCs) were enumerated in HIV-infected children on ART. Memory B cell responses were expressed as numbers of antibody secreting cells (ASCs) per million cultured peripheral blood mononuclear cells (PBMCs) seeded on the ELISPOT well. Each dot represents an average of test wells performed in triplicate. Horizontal bars represent median values. The broken horizontal lines in A–C represent median values in HIV-uninfected controls recruited as part of separate contemporaneous study reported elsewhere.10 The interquartile range for these controls has been incorporated in the y-axis except the upper quartile band for CbpA specific memory B cells of 44.2 that was not incorporated owing to axis break. PsaA specific memory B cells were not measured in the HIV-uninfected cohort. Comparisons were made using Friedman's test to evaluate the effect of ART across all time points.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4441108&req=5

fig3: Pneumococcal protein antigen specific IgG memory B cells increase after 12 months' antiretroviral therapy (ART) in HIV-infected Malawian children. Using an enzyme-linked immunospot (ELISPOT) assay, following the expansion of memory B cells with a cocktail of mitogens (standardized pansorbin cells, pokeweed mitogen extract and phosphothiolated CpG oligodeoxynucleotide 2006) for six days, (A) Choline binding protein A (CbpA), (B) Pneumococcal surface protein A (PspA), (C) Pneumolysin (Ply), and (D) Pneumococcal surface antigen A (PsaA) specific IgG antibody secreting cells (ASCs) were enumerated in HIV-infected children on ART. Memory B cell responses were expressed as numbers of antibody secreting cells (ASCs) per million cultured peripheral blood mononuclear cells (PBMCs) seeded on the ELISPOT well. Each dot represents an average of test wells performed in triplicate. Horizontal bars represent median values. The broken horizontal lines in A–C represent median values in HIV-uninfected controls recruited as part of separate contemporaneous study reported elsewhere.10 The interquartile range for these controls has been incorporated in the y-axis except the upper quartile band for CbpA specific memory B cells of 44.2 that was not incorporated owing to axis break. PsaA specific memory B cells were not measured in the HIV-uninfected cohort. Comparisons were made using Friedman's test to evaluate the effect of ART across all time points.
Mentions: In contrast to total B cell subsets, recovery in numbers of circulating memory B cells specific for four pneumococcal antigens (Choline binding protein A (CbpA), Pneumococcal surface protein A (PspA), Pneumolysin (Ply) and Pneumococcal surface antigen A (PsaA)) only became apparent during the latter part of the 12 month observation period (P = 0.007, P = 0.02, P = 0.02, P = 0.001 respectively (Fig. 3)). Median values approached those seen in uninfected controls by 12 months for two of the three antigens for which control data were available (Fig. 3).

Bottom Line: The proportions of mature naïve B cells (CD19(+) CD10(-) CD27(-) CD21(hi)) and resting memory B cells (CD19(+) CD27(+) CD21(hi)) increased and apoptosis-prone mature activated B cells (CD19(+) CD21(lo) CD10(-)) decreased markedly by 12 months.These data show that, in chronically HIV-infected children receiving ART, improvement in B-cell memory profiles and function is slower than CD4(+) T-cells.This supports early initiation of ART and informs research into optimal timing of immunization with pneumococcal vaccines.

View Article: PubMed Central - PubMed

Affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.

No MeSH data available.


Related in: MedlinePlus