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Naïve B-cell Output in Hiv-infected and Hiv-uninfected Children

Payne, H; Chain, G; Adams, S; Hunter, P; Luckhurst, N; Gilmour, K; Lewis, J; ... Klein, N; + view all (2019) Naïve B-cell Output in Hiv-infected and Hiv-uninfected Children. AIDS Research and Human Retroviruses , 35 (1) 10.1089/AID.2018.0170. Green open access

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Abstract

BACKGROUND: In this study, we aimed to quantify KREC (kappa-deleting recombination excision circles) levels and naïve B-cell output in healthy HIV-uninfected children, compared with HIV-infected South African children, before and after starting ART (anti-retroviral therapy). SETTING: Samples were acquired from a Child Wellness Clinic (n=288 HIV-uninfected South African children, 2 weeks - 12 years) and the Children with HIV and Early Antiretroviral Therapy (CHER) trial (n=153 HIV-infected South African children, 7 weeks - 8 years). METHODS: Naïve B-cell output was estimated using a mathematical model combining KREC levels to reflect B-cell emigration into the circulation, flow cytometry measures of naïve un-switched B-cells to quantify total body naïve B-cells, and their rates of proliferation using the intracellular marker Ki67. RESULTS: Naïve B-cell output increases from birth to 1 year, followed by a decline and plateau into late childhood. HIV-infected children on or off ART had higher naïve B-cell outputs than their uninfected counterparts (p=0.01 and p=0.04). CONCLUSIONS: This is the first study to present reference ranges for measurements of KRECs and naïve B-cell output in healthy and HIV-infected children. Comparison between HIV-uninfected healthy children and HIV-infected children suggest that HIV may increase naïve B-cell output. Further work is required to fully understand the mechanisms involved and clinical value of measuring naïve B-cell output in children.  .

Type: Article
Title: Naïve B-cell Output in Hiv-infected and Hiv-uninfected Children
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/AID.2018.0170
Publisher version: https://doi.org/10.1089/AID.2018.0170
Language: English
Additional information: This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: HIV, ART, child, naïve B-cell output, bone marrow, KRECs
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10059017
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