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Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis [version 1; peer review: 1 approved, 2 approved with reservations]

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Title: Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis [version 1; peer review: 1 approved, 2 approved with reservations]
Authors: Lewin, A
Hamilton, S
Witkover, A
Langford, P
Nicholas, R
Chataway, J
Bangham, CR
Item Type: Journal Article
Abstract: 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 An underlying low-grade chronic intravascular haemolysis is a potential source of the iron whose deposition along blood vessels in multiple sclerosis plaques contributes to the neurodegeneration and consequent brain atrophy seen in progressive disease. Chelators of free serum iron will be ineffective in preventing this neurodegeneration, because the iron (Fe(2+)) is chelated by haemoglobin.
Issue Date: 15-Nov-2016
Date of Acceptance: 1-Nov-2016
URI: http://hdl.handle.net/10044/1/43863
DOI: 10.12688/wellcomeopenres.9967.1
ISSN: 2398-502X
Publisher: F1000Research
Journal / Book Title: Wellcome Open Research
Volume: 1
Copyright Statement: © 2016 Lewin A et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Multiple Sclerosis Trials Collaboration (MSTC)
Imperial College Trust
Medical Research Council (MRC)
Multiple Sclerosis Trials Collaboration (MSTC)
J P Moulton Charitable Foundation
Biotechnology and Biological Sciences Research Council (BBSRC)
Medical Research Council (MRC)
Funder's Grant Number: N/A
Keywords: Secondary progressive multiple sclerosis
brain atrophy
Publication Status: Published
Conference Place: England
Article Number: 10
Appears in Collections:Department of Brain Sciences