Abstract
BackgroundHuman 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.ResultsThe 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.ConclusionsThe 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.
Highlights
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)
Human T lymphotropic virus Type 1 (HTLV-1) persists lifelong in the host and is associated with two distinct types of disease: a range of chronic inflammatory diseases, of which the most commonly recognized is HTLV-1-associated myelopathy/tropic spastic paraparesis (HAM/TSP, abbreviated hereafter as HAM), and an aggressive T cell malignancy known as adult T cell leukaemia/lymphoma (ATLL)
The biomarkers identified here are potentially of clinical use, because they were associated with the presence of the disease, HAM, and gave additional discriminatory information to that provided by the proviral load
Summary
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). 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. Human T lymphotropic virus Type 1 (HTLV-1) persists lifelong in the host and is associated with two distinct types of disease: a range of chronic inflammatory diseases, of which the most commonly recognized is HTLV-1-associated myelopathy/tropic spastic paraparesis (HAM/TSP, abbreviated hereafter as HAM), and an aggressive T cell malignancy known as adult T cell leukaemia/lymphoma (ATLL). There is an urgent need for additional tools to aid in the diagnosis of HTLV-1-associated disease both clinically and epidemiologically
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