three plasma biomarkers of htlv-1-associated myelopathy/tropical spastic paraparesis

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MEETING ABSTRACT Open Access Three plasma biomarkers of HTLV-1-associated myelopathy/tropical spastic paraparesis Paul Kirk 1 , Aviva Witkover 2 , Alan Courtney 3 , Alexandra M Lewin 4 , Robin Wait 5 , Michael P Stumpf 1 , Sylvia Richardson 4 , Graham P Taylor 6 , Charles R Bangham 2* From 15th International Conference on Human Retroviruses: HTLV and Related Viruses Leuven and Gembloux, Belgium. 5-8 June 2011 The pathogenesis of HAM remains uncertain: the dis- ease is thought to be caused by the immune response to HTLV-1, possibly by bystander damage to neurons in the spinal cord. The strongest correlate of HAM in HTLV-1-infected individuals is the proviral load of HTLV-1, i.e. the percentage of peripheral blood mono- nuclear cells that carry the provirus. To aid in the differ- ential diagnosis of HAM, and to search for clues as to the pathogenetic mechanisms of the disease, we carried out SELDI mass spectrometry on plasma samples from 68 HTLV-1-positive individuals, 16 uninfected controls and 11 patients with secondary progressive MS. We identified three plasma protein biomarkers that are spe- cifically associated with HAM, independently of proviral load. The three proteins were identified by tandem mass spectrometry as b2-microglobulin, calgranulin B, and apolipoprotein A2. Using the two most strongly asso- ciated biomarkers, b2-microglobulin and calgranulin B, we derive a simple algorithm that correctly classified the disease status (presence or absence of HAM) in 81% of HTLV-1-infected subjects in the cohort. Author details 1 Centre for Bioinformatics, Division of Molecular Biosciences, Imperial College, London, SW7 2AZ, UK. 2 Department of Immunology, Wright- Fleming Institute, Imperial College, London, W2 1PG, UK. 3 Department of Clinical Biochemistry, Imperial Academic Health Sciences Centre, St Marys Hospital, London W2 1PG, UK. 4 Department of Epidemiology and Biostatistics, Imperial College, London, W2 1PG, UK. 5 Kennedy Institute of Rheumatology, Imperial College London, 65 Aspenlea Road, London W6 8LH, UK. 6 Department of Genitourinary Medicine and Communicable Diseases, Wright-Fleming Institute, Imperial College, London, W2 1PG, UK. Published: 6 June 2011 doi:10.1186/1742-4690-8-S1-A43 Cite this article as: Kirk et al.: Three plasma biomarkers of HTLV-1- associated myelopathy/tropical spastic paraparesis. Retrovirology 2011 8 (Suppl 1):A43. Submit your next manuscript to BioMed Central and take full advantage of: Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit * Correspondence: [email protected] 2 Department of Immunology, Wright-Fleming Institute, Imperial College, London, W2 1PG, UK Kirk et al. Retrovirology 2011, 8(Suppl 1):A43 http://www.retrovirology.com/content/8/S1/A43 © 2011 Kirk et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MEETING ABSTRACT Open Access

Three plasma biomarkers of HTLV-1-associatedmyelopathy/tropical spastic paraparesisPaul Kirk1, Aviva Witkover2, Alan Courtney3, Alexandra M Lewin4, Robin Wait5, Michael P Stumpf1,Sylvia Richardson4, Graham P Taylor6, Charles R Bangham2*

From 15th International Conference on Human Retroviruses: HTLV and Related VirusesLeuven and Gembloux, Belgium. 5-8 June 2011

The pathogenesis of HAM remains uncertain: the dis-ease is thought to be caused by the immune response toHTLV-1, possibly by bystander damage to neurons inthe spinal cord. The strongest correlate of HAM inHTLV-1-infected individuals is the proviral load ofHTLV-1, i.e. the percentage of peripheral blood mono-nuclear cells that carry the provirus. To aid in the differ-ential diagnosis of HAM, and to search for clues as tothe pathogenetic mechanisms of the disease, we carriedout SELDI mass spectrometry on plasma samples from68 HTLV-1-positive individuals, 16 uninfected controlsand 11 patients with secondary progressive MS. Weidentified three plasma protein biomarkers that are spe-cifically associated with HAM, independently of proviralload. The three proteins were identified by tandem massspectrometry as b2-microglobulin, calgranulin B, andapolipoprotein A2. Using the two most strongly asso-ciated biomarkers, b2-microglobulin and calgranulin B,we derive a simple algorithm that correctly classified thedisease status (presence or absence of HAM) in 81% ofHTLV-1-infected subjects in the cohort.

Author details1Centre for Bioinformatics, Division of Molecular Biosciences, ImperialCollege, London, SW7 2AZ, UK. 2Department of Immunology, Wright-Fleming Institute, Imperial College, London, W2 1PG, UK. 3Department ofClinical Biochemistry, Imperial Academic Health Sciences Centre, St Mary’sHospital, London W2 1PG, UK. 4Department of Epidemiology andBiostatistics, Imperial College, London, W2 1PG, UK. 5Kennedy Institute ofRheumatology, Imperial College London, 65 Aspenlea Road, London W68LH, UK. 6Department of Genitourinary Medicine and CommunicableDiseases, Wright-Fleming Institute, Imperial College, London, W2 1PG, UK.

Published: 6 June 2011

doi:10.1186/1742-4690-8-S1-A43Cite this article as: Kirk et al.: Three plasma biomarkers of HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology 2011 8(Suppl 1):A43.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

* Correspondence: [email protected] of Immunology, Wright-Fleming Institute, Imperial College,London, W2 1PG, UK

Kirk et al. Retrovirology 2011, 8(Suppl 1):A43http://www.retrovirology.com/content/8/S1/A43

© 2011 Kirk et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.