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May 6, 2018

ESPID 2018

NAIVE B-CELL OUTPUT IN HEALTHY AND HIV-INFECTED CHILDREN FROM SOUTH AFRICA AND THE UK

;

Payne, H.;

CHAIN, G.;

Adams, S.;

Hunter, P.;

Luckhurst, N.;

Gilmour, K.;

Lewis, J.;

Babiker, A.;

Cotton, M.;

Violari, A.;

Gibb, D.;

Callard, R.;

Klein, N.

Abstract

Abstract

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Keywords

Abstract

Background: In this study, we aimed to quantify healthy ranges of naïve B-cell output and KREC (kappa-deleting recombination excision circles) levels. Additionally, we sought to determine the dynamics of naïve B-cell output in ART (anti-retroviral therapy)-treated HIV-positive children in South Africa and the UK. Setting: Samples were from a Child Wellness Clinic (n=288 HIV-uninfected South African children, 2 weeks – 12 years), the Children with HIV and Early Antiretroviral Therapy (CHER) trial (n=218 HIV-infected South African children, 7 weeks - 8 years) and from GOSH (Great Ormond Street Hospital) (n=16 HIV-uninfected British children, 6 - 18 years). Methods: Naïve B-cell output was quantified using a mathematical model combining KREC levels to reflect B-cell emigration into the circulation, flow cytometry measures of naïve un-switched B-cells and their rates of proliferation using the marker Ki67. Results: Naïve B-cell output increases from birth to 1 year, followed by a decline. Comparison to British children revealed higher naïve B-cell outputs in South African children (p=0.013). HIV-infected children on ART had higher naïve B-cell outputs than their uninfected counterparts (p=0.010), and there was a trend toward lower naïve B-cell output with ART-interruption compared to continuous ART. Conclusions: The results of this study suggest that HIV in the context of ART can influence B-cell output, which differs between UK and African children. Further work is required to fully understand the causes and consequences of HIV on B-cell dynamics in children.

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© Copyright 2019 Morressier GmbH.
All rights reserved.