Kirk, Paul, Witkover, Aviva, Courtney, Alan, Lewin, Alexandra M., Wait, Robin, Stumpf, M. P. H. (Michael P. H.), Richardson, Sylvia, Taylor, G. P. (Graham P.) and Bangham, C. R. M. (Charles R. M.) (2011) Plasma proteome analysis in HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology, Vol.8 . p. 81. doi:10.1186/1742-4690-8-81

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Abstract

Background: Human T lymphotropic virus Type 1 (HTLV-1) causes a chronic inflammatory disease of the central
nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM) which resembles
chronic spinal forms of multiple sclerosis (MS). The pathogenesis of HAM remains uncertain. To aid in the
differential diagnosis of HAM and to identify pathogenetic mechanisms, we analysed the plasma proteome in
asymptomatic HTLV-1 carriers (ACs), patients with HAM, uninfected controls, and patients with MS. We used
surface-enhanced laser desorption-ionization (SELDI) mass spectrometry to analyse the plasma proteome in 68
HTLV-1-infected individuals (in two non-overlapping sets, each comprising 17 patients with HAM and 17 ACs), 16
uninfected controls, and 11 patients with secondary progressive MS. Candidate biomarkers were identified by
tandem Q-TOF mass spectrometry.
Results: The concentrations of three plasma proteins - high [β2-microglobulin], high [Calgranulin B], and low
[apolipoprotein A2] - were specifically associated with HAM, independently of proviral load. The plasma [β2-
microglobulin] was positively correlated with disease severity.
Conclusions: The results indicate that monocytes are activated by contact with activated endothelium in HAM.
Using β2-microglobulin and Calgranulin B alone we derive a diagnostic algorithm that correctly classified the
disease status (presence or absence of HAM) in 81% of HTLV-1-infected subjects in the cohort.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre
Library of Congress Subject Headings (LCSH):	HTLV-I (Virus), Central nervous system -- Diseases -- Pathophysiology, Central nervous system -- Diseases -- Diagnosis
Journal or Publication Title:	Retrovirology
Publisher:	BioMed Central Ltd.
ISSN:	1742-4690
Official Date:	12 October 2011
Dates:	Date Event 12 October 2011 Published
Volume:	Vol.8
Page Range:	p. 81
DOI:	10.1186/1742-4690-8-81
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Wellcome Trust (London, England), National Institute for Health Research (Great Britain) (NIHR)
Grant number:	080871 (WT), 080713 (WT)

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