Lewin, A;
Hamilton, S;
Witkover, A;
Langford, P;
Nicholas, R;
Chataway, J;
Bangham, CRM;
(2016)
Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis.
Wellcome Open Research
, 1
, Article 10. 10.12688/wellcomeopenres.9967.1.
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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. FINDINGS: 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. Interpretation 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 (Fe2+) is chelated by haemoglobin.
| Type: | Article |
|---|---|
| Title: | Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.12688/wellcomeopenres.9967.1 |
| Publisher version: | http://dx.doi.org/10.12688/wellcomeopenres.9967.1 |
| Language: | English |
| Additional information: | © 2016 Lewin A et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A later version is available at http://discovery.ucl.ac.uk/1547571/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1529204 |
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