Article

Differentiation of HAM/TSP from patients with multiple sclerosis infected with HTLV-I

Neurological Service, Gaffree Guinle University Hospital, Federal University of Rio de Janeiro State, Rio de Janeiro, Brazil.
Neurology (Impact Factor: 8.29). 02/2007; 68(3):206-13. DOI: 10.1212/01.wnl.0000251300.24540.c4
Source: PubMed

ABSTRACT

To better differentiate patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) from patients with multiple sclerosis (MS) who are HTLV-I seropositive, we compared the HTLV-I antibodies and HTLV-I proviral DNA loads in CSF and peripheral blood mononuclear cells (PBMC).
Intrathecal synthesis of HTLV-I antibodies and HTLV-I proviral DNA loads in CSF and PBMC were measured and compared in 39 Brazilian patients: 17 HAM/TSP and 22 HTLV-I-seropositive non-HAM/TSP (7 with other neurologic diseases, 11 asymptomatic carriers, and 4 HTLV-I-seropositive patients with an MS-like phenotype). In addition, we followed immunologic and virologic markers in comparison to the clinical course (by Kurtzke Expanded Disability Status Scale) of seven patients (five with HAM/TSP and two with an MS-like phenotype) for a mean period of 16 (SD +/- 5) months.
The proviral load in CSF and PBMC was higher in HAM/TSP than in non-HAM/TSP patients, except in the two HTLV-I-seropositive patients with an MS-like phenotype that also fulfilled the criteria for HAM/TSP. Higher HTLV-I proviral DNA load in CSF was associated with the higher proviral DNA load in PBMC and lower intrathecal synthesis of HTLV-I antibodies. These laboratory findings remained stable during follow-up.
The high proviral load in peripheral blood mononuclear cells or in CSF or both may be a good marker of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and can differentiate patients with HAM/TSP from patients with multiple sclerosis infected with HTLV-I.

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    • "The mechanisms that lead to clinical manifestation in some individuals are still poorly understood. In this context, it is known that high proviral load is associated with disease outcome [6] [7] [8] [9] [10]. "
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    ABSTRACT: The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with both proliferative and inflammatory disorders. This virus causes a persistent infection, mainly in CD4+ T lymphocyte. The ability to persist in the host is associated with the virus capacity to evade the immune response and to induce infected T-cell proliferation, once the HTLV-1 maintains the infection mainly by clonal expansion of infected cells. There are several evidences that ORF-I encoded proteins, such as p12 and p8, play an important role in this context. The present study will review the molecular mechanisms that HTLV-1 ORF-I encoded proteins have to induce dysregulation of intracellular signaling, in order to escape from immune response and to increase the infected T-cell proliferation rate. The work will also address the impact of ORF-I mutations on the human host and perspectives in this study field.
    Full-text · Article · Nov 2015 · Journal of Immunology Research
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    • "Moreover, in HAM/TSP patients, the PVL CSF/PVL blood ratio was always higher than 1 in HAM/TSP and lower than 1 in AC [38] PVL in CSF inverse correlated with intrathecal synthesis of HTLV-1 antibodies (HTLV-1 AI) [12] . Another interesting point is that PVL in CSF combined to intrathecal synthesis of HTLV-1 antibodies analysis showed to be useful in discriminating between HAM/TSP and multiple sclerosis (MS) [13] . This is extremely important because HTLV and MS present very similar symptoms. "
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    ABSTRACT: Different human retroviruses, such as Human Immunodeficiency Virus (HIV) and Human T-cell Lymphotropic Virus (HTLV), can cause neurologic infection. However, a definitive diagnosis may be hampered by several factors. Quantification of the viral or proviral load in cerebrospinal fluid (CSF) may be helpful in the diagnosis of nervous system disorders due to retroviral infection and may influence the treatment approach. The present work discusses retrovirus infection and neurologic impairment, as well as the usefulness of the determination of the HIV and HTLV proviral or viral load in cerebrospinal fluid in cases of neurologic disorder, in light of recent advances in this field. This study also discusses the different molecular techniques for quantifying the proviral load (real-time quantitative PCR, droplet digital PCR, and semi-nested real-time reverse transcription PCR) that are currently available.
    Full-text · Article · Aug 2015 · Journal of Biomedical Science
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    • "Due to the high sensitivity and specificity and the ability to differentiate between specific viral proteins, the WB test can be valuable for assessing the intrathecal synthesis of anti-HTLV-1 Abs. In endemic areas, the use of a sensitive and specific biomarker may clarify the HAM/TSP diagnosis in mono or oligosymptomatic patients (Puccioni-Sohler et al. 2007, Slater et al. 2012). The aim of this study was to standardise the WB test (using paired CSF and serum samples) to detect specific intrathecal Abs for HAM/TSP diagnosis. "
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    ABSTRACT: Intrathecal synthesis of human T-lymphotropic virus type 1 (HTLV-1) antibodies (Abs) represents conclusive evidence of a specific immune response in the central nervous system of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. Western blotting (WB) for HTLV Abs in serum is a confirmatory test for HTLV-1 infection. The aim of this study was to standardise the Western blot to demonstrate the intrathecal pattern of Abs against HTLV-1 proteins in HAM/TSP patients. Paired cerebrospinal fluid (CSF) and serum samples were selected from 20 patients with definite HAM/TSP, 19 HTLV-1 seronegative patients and two HTLV-1 patients without definite HAM/TSP. The presence of reactive bands of greater intensity in the CSF compared to serum (or bands in only the CSF) indicated the intrathecal synthesis of anti-HTLV-1 Abs. All definite HAM/TSP patients presented with an intrathecal synthesis of anti-HTLV-1 Abs; these Abs were not detected in the control patients. The most frequent intrathecal targets of anti-HTLV-1 Abs were GD21, rgp46-I and p24 and, to a lesser extent, p19, p26, p28, p32, p36, p53 gp21 and gp46. The intrathecal immune response against env (GD21 and rgp46-I) and gag (p24) proteins represents the most important humoral pattern in HAM/TSP. This response may be used as a diagnostic marker, considering the frequent association of intrathecal anti-HTLV-1 Ab synthesis with HAM/TSP and the pathogenesis of this neurological disease.
    Full-text · Article · Sep 2013 · Memórias do Instituto Oswaldo Cruz
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