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{Asquith:2015:10.1371/journal.pcbi.1004355,
author = {Asquith, RE},
doi = {10.1371/journal.pcbi.1004355},
journal = {PLOS Computational Biology},
title = {Reconciling estimates of cell proliferation from stable isotope labeling experiments},
url = {http://dx.doi.org/10.1371/journal.pcbi.1004355},
volume = {11},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Stable isotope labeling is the state of the art technique for in vivo quantification of lymphocyte kinetics in humans. It has been central to a number of seminal studies, particularly in the context of HIV-1 and leukemia. However, there is a significant discrepancy between lymphocyte proliferation rates estimated in different studies. Notably, deuterated 2H2-glucose (D2-glucose) labeling studies consistently yield higher estimates of proliferation than deuterated water (D2O) labeling studies. This hampers our understanding of immune function and undermines our confidence in this important technique. Whether these differences are caused by fundamental biochemical differences between the two compounds and/or by methodological differences in the studies is unknown. D2-glucose and D2O labeling experiments have never been performed by the same group under the same experimental conditions; consequently a direct comparison of these two techniques has not been possible. We sought to address this problem. We performed both in vitro and murine in vivo labeling experiments using identical protocols with both D2-glucose and D2O. This showed that intrinsic differences between the two compounds do not cause differences in the proliferation rate estimates, but that estimates made using D2-glucose in vivo were susceptible to difficulties in normalization due to highly variable blood glucose enrichment. Analysis of three published human studies made using D2-glucose and D2O confirmed this problem, particularly in the case of short term D2-glucose labeling. Correcting for these inaccuracies in normalization decreased proliferation rate estimates made using D2-glucose and slightly increased estimates made using D2O; thus bringing the estimates from the two methods significantly closer and highlighting the importance of reliable normalization when using this technique.
AU  - Asquith,RE
DO  - 10.1371/journal.pcbi.1004355
PY  - 2015///
SN  - 1553-734X
TI  - Reconciling estimates of cell proliferation from stable isotope labeling experiments
T2  - PLOS Computational Biology
UR  - http://dx.doi.org/10.1371/journal.pcbi.1004355
UR  - http://hdl.handle.net/10044/1/25010
VL  - 11
ER  -
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