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. ISSN 1742-4690

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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 > Centre for Systems Biology
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
Date:	12 October 2011
Volume:	Vol.8
Page Range:	p. 81
Identification Number:	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)
References:	1. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N, Moritoyo T, Hashiguchi S, Ichinose M, Bangham CR, Izumo S, Osame M: Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. J Neurovirol 1998, 4:586-593. 2. Bangham CRM, Meekings K, Toulza F, Nejmeddine M, Majorovits E, Asquith B, Taylor GP: The immune control of HTLV-1 infection: selection forces and dynamics. Frontiers in Bioscience 2009, 14:2889-2903. 3. Goon PK, Hanon E, Igakura T, Tanaka Y, Weber JN, Taylor GP, Bangham CR: High frequencies of Th1-type CD4(+) T cells specific to HTLV-1 Env and Tax proteins in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. Blood 2002, 99:3335-3341. 4. Goon PK, Igakura T, Hanon E, Mosley AJ, Asquith B, Gould KG, Taylor GP, Weber JN, Bangham CR: High circulating frequencies of tumor necrosis factor alpha- and interleukin-2-secreting human T-lymphotropic virus type 1 (HTLV-1)-specific CD4+ T cells in patients with HTLV-1-associated neurological disease. J Virol 2003, 77:9716-9722. 5. Toulza F, Heaps A, Tanaka Y, Taylor GP, Bangham CR: High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with HTLV-1- specific CTL response. Blood 2008, 111:5047-5053. 6. Yu F, Itoyama Y, Fujihara K, Goto I: Natural killer (NK) cells in HTLV-Iassociated myelopathy/tropical spastic paraparesis-decrease in NK cell subset populations and activity in HTLV-I seropositive individuals. J Neuroimmunol 1991, 33:121-128. 7. Saito M, Braud VM, Goon P, Hanon E, Taylor GP, Saito A, Eiraku N, Tanaka Y, Usuku K, Weber JN, et al: Low frequency of CD94/NKG2A+ T lymphocytes in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis, but not in asymptomatic carriers. Blood 2003, 102:577-584. 8. Yamano Y, Cohen CJ, Takenouchi N, Yao K, Tomaru U, Li HC, Reiter Y, Jacobson S: Increased expression of human T lymphocyte virus type I (HTLV-I) Tax11-19 peptide-human histocompatibility leukocyte antigen A*201 complexes on CD4+ CD25+ T Cells detected by peptide-specific, major histocompatibility complex-restricted antibodies in patients with HTLV-I-associated neurologic disease. J Exp Med 2004, 199:1367-1377. 9. Yamano Y, Nagai M, Brennan M, Mora CA, Soldan SS, Tomaru U, Takenouchi N, Izumo S, Osame M, Jacobson S: Correlation of human T-cell lymphotropic virus type 1 (HTLV-1) mRNA with proviral DNA load, virusspecific CD8(+) T cells, and disease severity in HTLV-1-associated myelopathy (HAM/TSP). Blood 2002, 99:88-94. 10. Asquith B, Mosley AJ, Heaps A, Tanaka Y, Taylor GP, McLean AR, Bangham CR: Quantification of the virus-host interaction in human T lymphotropic virus I infection. Retrovirology 2005, 2:75. 11. Meekings KN, Leipzig J, Bushman FD, Taylor GP, Bangham CR: HTLV-1 integration into transcriptionally active genomic regions is associated with proviral expression and with HAM/TSP. PLoS Pathog 2008, 4: e1000027. 12. Storey J: A direct approach to false discovery rates. J Roy Stat Soc B 2002, 64:479-498. 13. Niederkofler EE, Tubbs KA, Kiernan UA, Nedelkov D, Nelson RW: Novel mass spectrometric immunoassays for the rapid structural characterization of plasma apolipoproteins. J Lipid Res 2003, 44:630-639. 14. Sokal RR, J RF: Biometry New York: W. H. Freeman; 2004. 15. Kay NE, Shanafelt TD: Prognostic factors in chronic lymphocytic leukemia. Curr Hematol Malig Rep 2007, 2:49-55. 16. Swan F, Velasquez WS, Tucker S, Redman JR, Rodriguez MA, McLaughlin P, Hagemeister FB, Cabanillas F: A new serologic staging system for largecell lymphomas based on initial beta 2-microglobulin and lactate dehydrogenase levels. J Clin Oncol 1989, 7:1518-1527. 17. Bergsagel PL: Individualizing therapy using molecular markers in multiple myeloma. Clin Lymphoma Myeloma 2007, 7:S170-174. 18. Fahey JL, Taylor JM, Detels R, Hofmann B, Melmed R, Nishanian P, Giorgi JV: The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type 1. N Engl J Med 1990, 322:166-172. 19. Leligdowicz A, Feldmann J, Jaye A, Cotten M, Dong T, McMichael A, Whittle H, Rowland-Jones S: Direct relationship between virus load and systemic immune activation in HIV-2 infection. J Infect Dis 2010, 201:114-122. 20. Simonsen AH, McGuire J, Podust VN, Davies H, Minthon L, Skoog I, Andreasen N, Wallin A, Waldemar G, Blennow K: Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer’s disease. Neurobiol Aging 2008, 29:961-968. 21. Bjerrum OW, Bach FW, Zeeberg I: Increased level of cerebrospinal fluid beta 2-microglobulin is related to neurologic impairment in multiple sclerosis. Acta Neurol Scand 1988, 78:72-75. 22. Carrieri PB, Indaco A, Maiorino A, Buscaino GA, Ponticiello A, Liberti A, Perrella O: Cerebrospinal fluid beta-2-microglobulin in multiple sclerosis and AIDS dementia complex. Neurol Res 1992, 14:282-283. 23. Ott M, Demisch L, Engelhardt W, Fischer PA: Interleukin-2, soluble interleukin-2-receptor, neopterin, L-tryptophan and beta 2-microglobulin levels in CSF and serum of patients with relapsing-remitting or chronicprogressive multiple sclerosis. J Neurol 1993, 241:108-114. 24. Hessian PA, Edgeworth J, Hogg N: MRP-8 and MRP-14, two abundant Ca (2+)-binding proteins of neutrophils and monocytes. J Leukoc Biol 1993, 53:197-204. 25. Passey RJ, Xu K, Hume DA, Geczy CL: S100A8: emerging functions and regulation. J Leukoc Biol 1999, 66:549-556. 26. Frosch M, Strey A, Vogl T, Wulffraat NM, Kuis W, Sunderkotter C, Harms E, Sorg C, Roth J: Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticularonset juvenile rheumatoid arthritis. Arthritis Rheum 2000, 43:628-637. 27. Odink K, Cerletti N, Bruggen J, Clerc RG, Tarcsay L, Zwadlo G, Gerhards G, Schlegel R, Sorg C: Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis. Nature 1987, 330:80-82. 28. Rugtveit J, Brandtzaeg P, Halstensen TS, Fausa O, Scott H: Increased macrophage subset in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes. Gut 1994, 35:669-674. 29. Roth J, Teigelkamp S, Wilke M, Grun L, Tummler B, Sorg C: Complex pattern of the myelo-monocytic differentiation antigens MRP8 and MRP14 during chronic airway inflammation. Immunobiology 1992, 186:304-314. 30. Goebeler M, Roth J, Burwinkel F, Vollmer E, Bocker W, Sorg C: Expression and complex formation of S100-like proteins MRP8 and MRP14 by macrophages during renal allograft rejection. Transplantation 1994, 58:355-361. 31. Bealer JF, Colgin M: S100A8/A9: a potential new diagnostic aid for acute appendicitis. Acad Emerg Med 2010, 17:333-336. 32. Iwasaki Y: Human T cell leukemia virus type I infection and chronic myelopathy. Brain Pathol 1993, 3:1-10. 33. Martin-Campos JM, Escola-Gil JC, Ribas V, Blanco-Vaca F: Apolipoprotein AII, genetic variation on chromosome 1q21-q24, and disease susceptibility. Curr Opin Lipidol 2004, 15:247-253. 34. Castellani LW, Navab M, Van Lenten BJ, Hedrick CC, Hama SY, Goto AM, Fogelman AM, Lusis AJ: Overexpression of apolipoprotein AII in transgenic mice converts high density lipoproteins to proinflammatory particles. J Clin Invest 1997, 100:464-474. 35. Thompson PA, Berbee JF, Rensen PC, Kitchens RL: Apolipoprotein A-II augments monocyte responses to LPS by suppressing the inhibitory activity of LPS-binding protein. Innate Immun 2008, 14:365-374. 36. Semmes OJ, Cazares LH, Ward MD, Qi L, Moody M, Maloney E, Morris J, Trosset MW, Hisada M, Gygi S, Jacobson S: Discrete serum protein signatures discriminate between human retrovirus-associated hematologic and neurologic disease. Leukemia 2005, 19:1229-1238. 37. Churchill GA: Using ANOVA to analyze microarray data. Biotechniques 2004, 37:173-175, 177. 38. Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc B 1995, 57:289-300. 39. Friedman J, Hastie T, Tibshirani R: Regularization paths for generalized linear models via coordinate descent. J Stat Softw 2010, 33:1-22. 40. Tibshirani R: Regression shrinkage and selection via the Lasso. Journal of the Royal Statistical Society Series B-Methodological 1996, 58:267-288. 41. Saeys Y, Abeel T, Van de Peer Y: Robust feature selection using ensemble feature selection techniques. In Lecture Notes in Computer Science. Volume 5212. Berlin/Heidelberg: Springer; 2008:313-325. 42. Wait R, Miller I, Eberini I, Cairoli F, Veronesi C, Battocchio M, Gemeiner M, Gianazza E: Strategies for proteomics with incompletely characterized genomes: the proteome of Bos taurus serum. Electrophoresis 2002, 23:3418-3427. 43. Searle BC: Scaffold: a bioinformatic tool for validating MS/MS-based proteomic studies. Proteomics 2010, 10:1265-1269.
URI:	http://wrap.warwick.ac.uk/id/eprint/39474

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