Imperial College London
Alternate

Dr Becca Asquith

Faculty of Medicine, Department of Infectious Disease

Professor of Mathematical Immunology
 
 
 
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Contact

 

+44 (0)20 7594 3731b.asquith

 
 
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Location

 

112Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lahoz-Beneytez:2017:10.3389/fimmu.2017.00474,
author = {Lahoz-Beneytez, J and Schaller, S and Macallan, D and Eissing, T and Niederalt, C and Asquith, B},
doi = {10.3389/fimmu.2017.00474},
journal = {Frontiers in Immunology},
title = {Physiologically based simulations of deuterated glucose for quantifying cell turnover in humans},
url = {http://dx.doi.org/10.3389/fimmu.2017.00474},
volume = {8},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - In vivo [6,6-2H2]-glucose labeling is a state-of-the-art technique for quantifying cell proliferation and cell disappearance in humans. However, there are discrepancies between estimates of T cell proliferation reported in short (1-day) versus long (7-day) 2H2-glucose studies and very-long (9-week) 2H2O studies. It has been suggested that these discrepancies arise from underestimation of true glucose exposure from intermittent blood sampling in the 1-day study. Label availability in glucose studies is normally approximated by a “square pulse” (Sq pulse). Since the body glucose pool is small and turns over rapidly, the availability of labeled glucose can be subject to large fluctuations and the Sq pulse approximation may be very inaccurate. Here, we model the pharmacokinetics of exogenous labeled glucose using a physiologically based pharmacokinetic (PBPK) model to assess the impact of a more complete description of label availability as a function of time on estimates of CD4+ and CD8+ T cell proliferation and disappearance. The model enabled us to predict the exposure to labeled glucose during the fasting and de-labeling phases, to capture the fluctuations of labeled glucose availability caused by the intake of food or high-glucose beverages, and to recalculate the proliferation and death rates of immune cells. The PBPK model was used to reanalyze experimental data from three previously published studies using different labeling protocols. Although using the PBPK enrichment profile decreased the 1-day proliferation estimates by about 4 and 7% for CD4 and CD8+ T cells, respectively, differences with the 7-day and 9-week studies remained significant. We conclude that the approximations underlying the “square pulse” approach—recently suggested as the most plausible hypothesis—only explain a component of the discrepancy in published T cell proliferation rate estimates.
AU  - Lahoz-Beneytez,J
AU  - Schaller,S
AU  - Macallan,D
AU  - Eissing,T
AU  - Niederalt,C
AU  - Asquith,B
DO  - 10.3389/fimmu.2017.00474
PY  - 2017///
SN  - 1664-3224
TI  - Physiologically based simulations of deuterated glucose for quantifying cell turnover in humans
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2017.00474
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000400312600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/48558
VL  - 8
ER  -
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