Introduction The seroprevalence of human T-cell leukemia virus type 1 (HTLV-1) is very high among Brazilians (~1:200). HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the most common neurological complication of HTLV-1 infection. HAM/TSP can present with an acute/subacute form of longitudinally extensive myelitis, which can be confused with lesions seen in aquaporin-4 antibody (AQP4-Ab) positive neuromyelitis optica spectrum disorders (NMOSD) on MRI. Moreover, clinical attacks in patients with NMOSD have been shown to be preceded by viral infections in around 30% of cases. Objective To evaluate the frequency of AQP4-Ab in patients with HAM/TSP. To evaluate the frequency of HTLV-1 infection in patients with NMOSD. Patients and Methods 23 Brazilian patients with HAM/TSP, 20 asymptomatic HTLV-1+ serostatus patients, and 34 with NMOSD were tested for AQP4-Ab using a standardized recombinant cell based assay. In addition, all patients were tested for HTLV-1 by ELISA and Western blotting. Results 20/34 NMOSD patients were positive for AQP4-Ab but none of the HAM/TSP patients and none of the asymptomatic HTLV-1 infected individuals. Conversely, all AQP4-Ab-positive NMOSD patients were negative for HTLV-1 antibodies. One patient with HAM/TSP developed optic neuritis in addition to subacute LETM; this patient was AQP4-Ab negative as well. Patients were found to be predominantly female and of African descent both in the NMOSD and in the HAM/TSP group; Osame scale and expanded disability status scale scores did not differ significantly between the two groups. Conclusions Our results argue both against a role of antibodies to AQP4 in the pathogenesis of HAM/TSP and against an association between HTLV-1 infection and the development of AQP4-Ab. Moreover, the absence of HTLV-1 in all patients with NMOSD suggests that HTLV-1 is not a common trigger of acute attacks in patients with AQP4-Ab positive NMOSD in populations with high HTLV-1 seroprevalence.
References
[1]
Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG (1999) The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 53: 1107–1114.
[2]
Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, et al. (2012) Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflammation 9: 14.
[3]
Lennon VA, Wingerschuk DM, Kryzer TJ, Piltock SJ, Lucchinetti CF, et al. (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364: 2106–2112.
[4]
Jarius S, Wildemann B (2010) AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol 6: 383–392.
[5]
Pittock SJ, Lennon VA, de Seze J, Vermersch P, Homburger HA, et al. (2008) Neuromyelitis optica and non-organ-specific autoimmunity. Arch Neurol 65: 78–83.
[6]
Matiello M, Lennon VA, Jacob A, Pittock SJ, Lucchinetti CF, et al. (2008) NMO-IgG predicts the outcome of recurrent optic neuritis. Neurology 70: 2197–2200.
[7]
Jarius S, Frederikson J, Waters P, Paul F, Akman-Demir G, et al. (2010) Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis. J Neurol Sci 298: 158–162.
[8]
Petzold A, Pittock S, Lennon V, Maggiore C, Weinshenker BG, et al. (2010) Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis. J Neurol Neurosurg Psychiatry 81: 109–111.
[9]
Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG (2007) The spectrum of neuromyelitis optica. Lancet Neurol 6: 805–815.
[10]
Matsuoka M, Jeang KT (2007) Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nat Rev Cancer 7: 270–280.
[11]
Kaplan JE, Osame M, Kubota H, Igata A, Nishitani H, et al. (1990) The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I. J Acquir Immune Defic Syndr 3: 1096–1101.
[12]
Verdonck K, González E, Van Dooren S, Vandamme AM, Vanham G, et al. (2007) Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infectious Disease 7: 266–281.
[13]
Olindo S, Bonnan M, Merle H, Signate A, Smadja D, et al. (2010) Neuromyelitis optica associated with subacute human T-lymphotropic virus type 1 infection. J Clin Neurosci 17: 1449–1451.
[14]
Kasahata N, Shiota J, Miyazawa Y, Nakano I, Murayama S (2003) Acute human T-lymphotropic virus type 1-associated myelopathy: a clinicopathologic study. Arch Neurol 60: 873–876.
[15]
Koga M, Takahashi T, Kawai M, Negoro K, Kanda T (2009) Neuromyelitis optica with HTLV-1 infection: different from acute progressive HAM? Intern Med 48: 1157–1159.
[16]
Yoshida Y, Saiga T, Takahashi H, Hara A (1998) Optic neuritis and human T-lymphotropic virus type 1-associated myelopathy: a case report. Ophthalmologica 212: 73–76.
Kira JI (2003) Multiple sclerosis in the Japanese population. Lancet Neurol 2: 117–127.
[19]
Cabre P, Heinzlef O, Merle H, Buisson GG, Bera O, et al. (2001) MS and neuromyelitis optica in Martinique (French West Indies). Neurology 56: 507–514.
[20]
Lana-Peixoto MA, Lana Peixoto MI (1992) Is multiple sclerosis in Brazil and Asia alike? Arq Neuropsiquiatr 50: 419–425.
[21]
Galv?o-Castro B, Loures L, Rodrigues LG, Sereno A, Ferreira Junior OC, et al. (1997) Distribution of human T-lymphotropic vírus type I among blood donors: a nationwide Brazilian study. Transfusion 37: 242–243.
[22]
Kashima S, Alcantara LC, Takayanagui OM, Cunha MA, Castro BG, et al. (2006) Distribution of human T cell lymphotropic virus type 1 (HTLV-1) subtypes in Brazil: genetic characterization of LTR and tax region. AIDS Res Hum Retroviruses 22: 953–959.
[23]
Papais-Alvarenga RM, Miranda-Santos CM, Puccioni-Sohler M, de Almeida AM, Oliveira S, et al. (2002) Optic neuromyelitis syndrome in Brazilian patients. J Neurol Neurosurg Psychiatry 73: 429–435.
[24]
Adoni T, Lino AM, da Gama PD, Apóstolos-Pereira SL, Marchiori PE, et al. (2010) Recurrent neuromyelitis optica in Brazilian patients: clinical, immunological, and neuroimaging characteristics. Mult Scler 16: 81–86.
[25]
Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33: 1444–1452.
[26]
Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, et al. (1986) HTLV-I associated myelopathy, a new clinical entity. Lancet 1: 1031–1032.
[27]
Brito JC, da Nóbrega PV (2003) Myelopathy: clinical considerations and etiological aspects. Arq Neuropsiquiatr 61: 816–821.
[28]
Casseb J, de Oliveira AC, Vergara MP, Montanheiro P, Bonasser F, et al. (2008) Presence of tropical spastic paraparesis/human T-cell lymphotropic virus type 1-associated myelopathy (TSP/HAM)-like among HIV-1-infected patients. J Med Virol 80: 392–398.
[29]
WHO (1989) Scientific Group on HTLV-I Infections and Associated Diseases, Kagoshima, Japan 10–15 December 1988: report. Manila, Philippines: World Health Organization Regional Office for the Western Pacific. pp. 4–6.
[30]
Wingerchuk DM (2007) Diagnosis and treatment of neuromyelitis optica. Neurologist 13: 2–11.
[31]
Jarius S, Probst C, Borowski K, Franciotta D, Wildemann B, et al. (2010) Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci 291: 52–56.
[32]
Matsumoto M, Sugimoto M, Nakashima H, Imamura F, Kawano O, et al. (1990) Spontaneous T cell proliferation and release of soluble interleukin-2 receptors in patients with HTLV-I-associated myelopathy. Am J Trop Med Hyg 42: 365–373.
[33]
Murphy EL, Figueroa JP, Gibbs WN, Brathwaite A, Holding-Cobham M, et al. (1989) Sexual transmission of human T-lymphotropic virus type I (HTLV-I). Ann Intern Med 111: 555–560.
[34]
Haines JL, Bradford Y, Garcia ME, Reed AD, Neumeister E, et al. (2002) Multiple susceptibility loci for multiple sclerosis. Hum Mol Genet 11: 2251–2256.
[35]
Kanamori Y, Nakashima I, Takai Y, Nishiyama S, Kuroda H, et al. (2011) Pain in neuromyelitis optica and its effect on quality of life: a cross-sectional study. Neurology 77: 652–658.
[36]
Jarius S, Paul F, Franciotta D, Ruprecht K, Ringelstein M, et al. (2011) Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci 306: 82–90.
[37]
Bergamaschi R, Tonietti S, Franciotta D, Candeloro E, Tavazzi E, et al. (2004) Oligoclonal bands in Devic’s neuromyelitis optica and multiple sclerosis: differences in repeated cerebrospinal fluid examinations. Mult Scler 10: 2–4.