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

Autor: Iwajomo OH; 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., Moons P; Department of Pediatrics, University of Malawi College of Medicine, Blantyre, Malawi., Nkhata R; Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., Mzinza D; Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., Ogunniyi AD; Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, Australia., Williams NA; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom., Heyderman RS; 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., Finn A; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom. Electronic address: adam.finn@bristol.ac.uk.
Jazyk: angličtina
Zdroj: The Journal of infection [J Infect] 2015 Jun; Vol. 70 (6), pp. 616-23. Date of Electronic Publication: 2014 Nov 01.
DOI: 10.1016/j.jinf.2014.10.011
Abstrakt: Objective: Despite CD4(+) count restoration and viral load suppression with antiretroviral therapy (ART), HIV-infected children remain at increased risk of life-threatening infections including invasive pneumococcal disease (IPD). We therefore investigated whether persistent susceptibility to IPD following ART is associated with incomplete recovery of B-cell function.
Methods: 41 HIV-infected Malawian children commencing ART were followed-up for a 1 year period during which time blood samples were collected at 0, 3, 6 and 12 months for comprehensive immunophenotyping and pneumomococcal-specific Memory B-cell Enzyme-Linked Immunospot assays. In addition, nasopharyngeal swab samples were cultured to determine pneumococcal carriage rates.
Results: Normalization of major lymphocyte subsets such as CD4(+) percentages was evident following 3 months of ART. 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. However, in the context of high nasopharyngeal pneumococcal carriage rates (83%), restoration of pneumococcal protein antigen-specific B-cell memory was more delayed.
Conclusions: 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.
(Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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