Imperial College London
Alternate

ProfessorPaulLangford

Faculty of Medicine, Department of Infectious Disease

Professor of Paediatric Infectious Diseases
 
 
 
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Contact

 

+44 (0)20 7594 3359p.langford Website

 
 
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Location

 

236Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lewin:2019:10.12688/wellcomeopenres.9967.2,
author = {Lewin, A and Hamilton, S and Witkover, A and Langford, P and Nicholas, R and Chataway, J and Bangham, CRM},
doi = {10.12688/wellcomeopenres.9967.2},
journal = {Wellcome Open Research},
title = {Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis [version 2; peer review: 3 approved]},
url = {http://dx.doi.org/10.12688/wellcomeopenres.9967.2},
volume = {1},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: A major cause of disability in secondary progressive multiple sclerosis (SPMS) is progressive brain atrophy, whose pathogenesis is not fully understood. The objective of this study was to identify protein biomarkers of brain atrophy in SPMS. Methods: We used surface-enhanced laser desorption-ionization time-of-flight mass spectrometry to carry out an unbiased search for serum proteins whose concentration correlated with the rate of brain atrophy, measured by serial MRI scans over a 2-year period in a well-characterized cohort of 140 patients with SPMS.  Protein species were identified by liquid chromatography-electrospray ionization tandem mass spectrometry. Results: There was a significant (p<0.004) correlation between the rate of brain atrophy and a rise in the concentration of proteins at 15.1 kDa and 15.9 kDa in the serum.  Tandem mass spectrometry identified these proteins as alpha-haemoglobin and beta-haemoglobin, respectively.  The abnormal concentration of free serum haemoglobin was confirmed by ELISA (p<0.001).  The serum lactate dehydrogenase activity was also highly significantly raised (p<10-12) in patients with secondary progressive multiple sclerosis.  Conclusions: The results are consistent with the following hypothesis. In progressive multiple sclerosis, low-grade chronic intravascular haemolysis releases haemoglobin into the serum; the haemoglobin is subsequently translocated into the central nervous system (CNS) across the damaged blood-brain barrier.  In the CNS, the haemoglobin and its breakdown products, including haem and iron, contribute to the neurodegeneration and consequent brain atrophy seen in progressive disease. We postulate that haemoglobin is a source of the iron whose deposition along blood vessels in multiple sclerosis plaques is associated with neurodegeneration.  If so, then chelators of haemoglobin, rather than chelators of free serum iron, may be effective in preventing this neurodegeneration.
AU  - Lewin,A
AU  - Hamilton,S
AU  - Witkover,A
AU  - Langford,P
AU  - Nicholas,R
AU  - Chataway,J
AU  - Bangham,CRM
DO  - 10.12688/wellcomeopenres.9967.2
PY  - 2019///
SN  - 2398-502X
TI  - Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis [version 2; peer review: 3 approved]
T2  - Wellcome Open Research
UR  - http://dx.doi.org/10.12688/wellcomeopenres.9967.2
UR  - http://hdl.handle.net/10044/1/75165
VL  - 1
ER  -
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