Autoimmune syndrome in the tropical spastic paraparesis/myelopathy associated with human T-lymphotropic virus infections
Keywords:
paraparesis, spastic, human T-lymphotropic virus 1, primateT-lymphotropic virus 1, spinal cord, autoantibodies, autoimmunity, molecular mimicry
Abstract
Introduction. Previous reports have given evidence that in tropical spastic paraparesis (TSP)/ human T-lymphotrophic virus (HTLV-I)-associated myelopathy (HAM), an autoimmune process occurs as part of its pathogenesis.Objective. The roles of autoimmunity and the molecular mimicry was evaluated in TSP/HAM
patients.
Materials and methods. Plasma samples were characterized from patients in the Pacific coastal region of Colombia. Thirty-seven were identified as TSP/HAM, 10 were diagnosed with adult Tcell leukemia virus, 22 were asymptomatic carriers but seropositive for HTLV-I and 20 were seronegative and served as negative controls. Plasmatic levels of the following were determined: antinuclear antibody (ANA) levels, anticardiolipine-2 (ACL_2), interferon- (IFN-??) and interleukin- 4 (IL-4). Using Western blot, the crossreactivity of the seropositive and seronegative samples was evaluated against proteins extracted from several central nervous system components of non infected Wistar rats. The HTLV-I seropositive plasmas were crossreacted with a monoclonal tax (LT4 anti-taxp40) from spinal cord neurons of non infected Wistar rats.
Results. Of the TSP/HAM patients, 70.2% were reactive against ANA and 83.8% against ACL- 2, in contrast with those ATL and asymptomatic seropositives subjects that were not reactive (P<0.001). Moreover, 70.3% had detectable levels of IFN and 43.2% had detectable IL-4. LT4 anti-taxp40 and plasma of TSP/HAM exhibited cross reactivity with a MW 33-35 kDa protein from the rat spinal cord nuclei. Conclusion. Support was provided for the existence of an autoimmune syndrome mediated by molecular mimicry; the syndrome was responsible for some of the axonal degeneration observed in TSP/HAM patients.
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References
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18. García-Vallejo F, Domínguez MC, Tamayo O. Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy. Braz J Med Biol Res. 2005;38:241-50.
19. Tanaka Y, Zeng L, Shiraki H, Shida H, Tozawa H. Identification of a neutralization epitope on the envelope gp46 antigen of human T cell leukemia virus type I and induction of neutralizing antibody by peptide immunization. J Immunol. 1991;147:354-60.
20. Lee B, Tanaka Y, Tozawa H. Monoclonal antibody defining tax protein of human T-cell leukemia virus type- I. Tohoku J Exp Med.1989;157:1-11.
21. Burnette WN. “Western blotting”: Electroforetic transfer of proteins from sodium dodecyl sulfate-polyacrilamide gels to unmodified nitrocellulose and radiographic detection with antibody and radiodinated protein. Anal Biochem. 1981;112:195-203.
22. Barin F, M’Boup S, Denis F, Kanki P, Allan JS, Lee TH, et al. Serological evidence for virus related to simian T-lymphotropic retrovirus III in residents of West Africa. Lancet. 1985;2:1387-9.
23. Hsu S, Raine L, Fanger H. Use of avidine-biotineperoxidase complex (ABC) in immnuperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedure. J. Histochem Cytochem. 1981;29:577.
24. Shi SR, Iman A, Young L, Cote R, Taylor CR. Antigen retrieval immunohistochemistry under the influenza of using monoclonal antibodies. J Histochem Cytochem. 1995; 43:193-201.
25. Ochi H, Wu XM, Osoegawa M, Horiuchi I, Minohara M, Murai H, et al. Tc1/Tc2 and Th1/Th2 balance in Asian and Western types of multiple sclerosis, HTLV-Iassociated myelopathy/tropical spastic paraparesis and hyper-IgEaemic myelitis. J Neuroimmunol. 2001; 119: 297-305.
26. Wu X, Osoegawa M, Yamasaki K, Kawano Y, Ochi H, Horiuchi I, et al. Flow cytometric differentiation of Asian and Western types of multiple sclerosis, HTLV- 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and hyperIgEaemic myelitis by analyses of memory CD4 positive T cell subsets and NK cell subsets. J Neurol Sci. 2000;177:24-31.
27. Horiuchi I, Kawano Y, Yamasaki K, Minohara M, Furue M, Taniwaki T, et al. Th1 dominance in HAM/ TSP and the optico-spinal form of multiple sclerosis versus Th2 dominance in mite antigen-specific IgE myelitis. J Neurol Sci. 2000;172:17-24.
28. Azran I, Schavinsky-Khrapunsky Y, Aboud M. Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity. Retrovirology. 2004;1:20-43
29. Barmak K, Harhaj E, Grant C, Alefantis T, Wigdahl B. Human T cell leukemia virus type I-induced disease: pathways to cancer and neurodegeneration. Virology. 2003;308:1-12.
30. Levin MC, Lee SM, Morcos Y, Brady J, Stuart J. Cross-reactivity between immunodominant human T lymphotropic virus type I tax and neurons: implications for molecular mimicry. J Infect Dis. 2002;186:1514-7
31. Lee SM, Dunnavant FD, Jang H, Zunt J, Levin MC. Autoantibodies that recognize functional domains of hnRNPA1 implicate molecular mimicry in the pathogenesis of neurological disease. Neurosci Lett. 2006;401:188-93.
32. Caporali R, Bugatti S, Bruschi E, Cavagna L, Montecucco C. Autoantibodies to heterogeneous nuclear ribonucleoproteins. Autoimmunity. 2005; 38: 25-32.
33. Princler GL, Julias JG, Hughes SH, Derse D. Roles of viral and cellular proteins in the expression of alternatively spliced HTLV-1 pX mRNAs. Virology. 2003;317:136-45.
34. Kress E, Hachem BH, Bex F, Gazzolo L, Duc M. Critical role of hnRNP A1 in HTLV-1 replication in human transformed T lymphocytes. Retrovirology. 2005;2:1-8.
2. Vernant JC, Maurs L, Gessain A, Barin F, Gout O, Delaporte JM, et al. Endemic tropical spastic paraparesis associated with human T-lymphotropic virus type I: a clinical and seroepidemiological study of 25 cases. Ann Neurol. 1987;21:123-30.
3. Osame M, Matsumoto M, Usuku K, Izumo S, Ijichi N, Amitani H, et al. Chronic progressive myelophathy associated with elevated antibodies to human Tlymphotropic virus type I and adult T-cell leukemia like cells. Ann Neurol. 1987;21:117-22.
4. Zaninovic V, Galindo J, Blank A. Paraparesia espástica tropical en Colombia. En: Enfermedades asociadas con el virus HTLV-I. Cali: Fundación MAR; 1992. p. 77-86.
5. Bartholomew C, Jack N, Edwards J, Charles W, Corbin D, Cleghorn FR, et al. HTLV-I serostatus of mothers of patients with adult T-cell leukemia and HTLVI- associated myelopathy/tropical spastic paraparesis. J Hum Virol. 1998;1:302-5.
6. Chávez M, Domínguez MC, Blank A, Quintana M, Eizuru Y, García-Vallejo F. Reconstrucción de la evolución molecular de la infección actual por el virus linfotrópico humano tipo I en Colombia. Biomédica. 2004;24:65-72.
7. Balcázar N, Sánchez G, García-Vallejo F. Sequence and phylogenetic analysis of Human T-Lymphotropic Virus type 1 from Tumaco, Colombia. Mem Inst Oswaldo Cruz. 2003 98:641-8
8. Trujillo JM, Concha M, Muñoz A, Bergonzoli G, Mora C, Borrero I, et al. Seroprevalence and cofactors of HTLV-I infection in Tumaco, Colombia. AIDS Res Hum Retroviruses. 1992;8:651-7.
9. Nakamura H, Kawakami A, Tominaga M, Hida A, Yamasaki S, Migita K, et al. Relationship between Sjögren’s syndrome and human T-lymphotropic virus type I infection: follow-up study of 83 patients. J Lab Clin Med. 2000;135:139-44.
10. Fox RI, Stern M, Michelson P. Update in Sjögren syndrome. Curr Opin Rheumatol. 2000;12:391-8.
11. Beger E, Deocharan E, Edelman M, Erblich B, Gu Y, Putterman C. A peptide DNA surrogate accelerates autoimmune manifestations and nephritis in lupus-prone mice. J Immunol. 2002;168:3617-26.
12. Bangham CR. HTLV-1 infections. J Clin Pathol. 2000;53:581-6.
13. Asquith B, Zhang Y, Mosley AJ, de Lara CM, Wallace DL, Worth A, et al. In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection. Proc Natl Acad Sci USA. 2007; 104:8035-40.
14. Verdonck K, González E, van Dooren S, Vandamme AM, Vanham G, Gotuzzo E. Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis. 2007;7:266-81.
15. Trujillo JR, Mclane MF, Lee TH, Essex M. Molecular mimicry between the human immunodeficiency virus type 1 gp120 V3 loop and human brain proteins. J Virol. 1993;67:7711-5.
16. Levin MC, Krikavsky M, Berck J, Foley S, Rosenfeld M, Dalmau J, et al. Neuronal molecular mimicry in immune-mediated neurologic disease. Ann Neurol. 1998;44:87-98.
17. Levin MC, Lee SM, Kalume F, Morcos Y, Dohan FC Jr, Hasty KA, et al. Autoimmunity due to molecular mimicry as a cause of neurological disease. Nat Med. 2002;8:509-13.
18. García-Vallejo F, Domínguez MC, Tamayo O. Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy. Braz J Med Biol Res. 2005;38:241-50.
19. Tanaka Y, Zeng L, Shiraki H, Shida H, Tozawa H. Identification of a neutralization epitope on the envelope gp46 antigen of human T cell leukemia virus type I and induction of neutralizing antibody by peptide immunization. J Immunol. 1991;147:354-60.
20. Lee B, Tanaka Y, Tozawa H. Monoclonal antibody defining tax protein of human T-cell leukemia virus type- I. Tohoku J Exp Med.1989;157:1-11.
21. Burnette WN. “Western blotting”: Electroforetic transfer of proteins from sodium dodecyl sulfate-polyacrilamide gels to unmodified nitrocellulose and radiographic detection with antibody and radiodinated protein. Anal Biochem. 1981;112:195-203.
22. Barin F, M’Boup S, Denis F, Kanki P, Allan JS, Lee TH, et al. Serological evidence for virus related to simian T-lymphotropic retrovirus III in residents of West Africa. Lancet. 1985;2:1387-9.
23. Hsu S, Raine L, Fanger H. Use of avidine-biotineperoxidase complex (ABC) in immnuperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedure. J. Histochem Cytochem. 1981;29:577.
24. Shi SR, Iman A, Young L, Cote R, Taylor CR. Antigen retrieval immunohistochemistry under the influenza of using monoclonal antibodies. J Histochem Cytochem. 1995; 43:193-201.
25. Ochi H, Wu XM, Osoegawa M, Horiuchi I, Minohara M, Murai H, et al. Tc1/Tc2 and Th1/Th2 balance in Asian and Western types of multiple sclerosis, HTLV-Iassociated myelopathy/tropical spastic paraparesis and hyper-IgEaemic myelitis. J Neuroimmunol. 2001; 119: 297-305.
26. Wu X, Osoegawa M, Yamasaki K, Kawano Y, Ochi H, Horiuchi I, et al. Flow cytometric differentiation of Asian and Western types of multiple sclerosis, HTLV- 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and hyperIgEaemic myelitis by analyses of memory CD4 positive T cell subsets and NK cell subsets. J Neurol Sci. 2000;177:24-31.
27. Horiuchi I, Kawano Y, Yamasaki K, Minohara M, Furue M, Taniwaki T, et al. Th1 dominance in HAM/ TSP and the optico-spinal form of multiple sclerosis versus Th2 dominance in mite antigen-specific IgE myelitis. J Neurol Sci. 2000;172:17-24.
28. Azran I, Schavinsky-Khrapunsky Y, Aboud M. Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity. Retrovirology. 2004;1:20-43
29. Barmak K, Harhaj E, Grant C, Alefantis T, Wigdahl B. Human T cell leukemia virus type I-induced disease: pathways to cancer and neurodegeneration. Virology. 2003;308:1-12.
30. Levin MC, Lee SM, Morcos Y, Brady J, Stuart J. Cross-reactivity between immunodominant human T lymphotropic virus type I tax and neurons: implications for molecular mimicry. J Infect Dis. 2002;186:1514-7
31. Lee SM, Dunnavant FD, Jang H, Zunt J, Levin MC. Autoantibodies that recognize functional domains of hnRNPA1 implicate molecular mimicry in the pathogenesis of neurological disease. Neurosci Lett. 2006;401:188-93.
32. Caporali R, Bugatti S, Bruschi E, Cavagna L, Montecucco C. Autoantibodies to heterogeneous nuclear ribonucleoproteins. Autoimmunity. 2005; 38: 25-32.
33. Princler GL, Julias JG, Hughes SH, Derse D. Roles of viral and cellular proteins in the expression of alternatively spliced HTLV-1 pX mRNAs. Virology. 2003;317:136-45.
34. Kress E, Hachem BH, Bex F, Gazzolo L, Duc M. Critical role of hnRNP A1 in HTLV-1 replication in human transformed T lymphocytes. Retrovirology. 2005;2:1-8.
How to Cite
1.
García F, Domínguez MC, Torres M, Tamayo Óscar, Criollo W, Quintana M, et al. Autoimmune syndrome in the tropical spastic paraparesis/myelopathy associated with human T-lymphotropic virus infections. Biomed. [Internet]. 2008 Dec. 1 [cited 2025 Apr. 4];28(4):510-22. Available from: https://revistabiomedicaorg.biteca.online/index.php/biomedica/article/view/56
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