1/20. Rapid development of subacute myelopathy in three organ transplant recipients after transmission of human T-cell lymphotropic virus type I from a single donor.BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) causes a subacute myelopathy in less than 5% of chronic carriers. However, the risk of neurologic disease appears to increase in persons infected through blood transfusion. methods: We report three recipients of solid organ transplants who developed a subacute myelopathy within 2 years after becoming infected with HTLV-I from a single asymptomatic HTLV-I donor. Genetic studies were performed in and sequences in proviral dna, and HTLV-I proviral load was measured by real-time quantitative polymerase chain reaction. RESULTS: HTLV-I sequences were obtained in two of these individuals, and they were almost identical and clustered within the Cosmopolitan A HTLV-I subtype, which indicates a common source. All typical changes in Tax amino acid sequence of the HTLV-I Cosmopolitan A were identified, plus two additional changes were noted. Although A has been associated with a greater risk of neurologic disease, both patients were positive for human leukocyte antigen-A*02, which is considered a protective factor. CONCLUSION: Rapid development of subacute myelopathy may occur in recipients of organ transplants from asymptomatic HTLV-I donors. A particular virulence of the virus strain, the large size of the virus inoculum, and the immunosuppressed condition after transplantation may have contributed to produce this unusual rapid development of HTLV-I associated myelopathy.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/20. Progressive spastic myelopathy in a patient co-infected with hiv-1 and HTLV-II: autoantibodies to the human homologue of rig in blood and cerebrospinal fluid.OBJECTIVE: Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are closely related human retroviruses. HTLV-I has been implicated in a chronic progressive myelopathy, known as tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). We sought to determine whether autoantibodies to brain antigens were present in the cerebrospinal fluid (CSF) of a patient with chronic progressive spastic myelopathy with evidence of both hiv-1 infection and HTLV-I/II seropositivity. DESIGN: A 54-year-old bisexual man with clinical features of HAM/TSP of over 20 years' duration was followed. methods: We applied discriminatory dna amplification (polymerase chain reaction) to distinguish HTLV-I from HTLV-II and to verify co-infection with hiv-1. The patient's CSF was used to screen a human brain cDNA expression library to identify antibodies directed against brain antigens. Autoreactive bacteriophage clones were isolated and sequenced. RESULTS: The patient was found to be co-infected with both hiv-1 and HTLV-II, but not with HTLV-I. HTLV-II proviral levels in the peripheral blood remained relatively constant, despite therapy with zidovudine. Prominent oligoclonal banding of immunoglobulins was present in the patient's CSF. A single repeatedly reactive cDNA clone was identified, by screening with CSF antibody, sequenced, and found to be the human homologue of the rat insulinoma gene, rig. CONCLUSIONS: HTLV-II infection may predispose to development of a HAM/TSP-like illness. Autoimmune mechanisms, such as autoantibody formation, may play a role in pathogenesis.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
3/20. Direct evidence for a chronic CD8 -T-cell-mediated immune reaction to tax within the muscle of a human T-cell leukemia/lymphoma virus type 1-infected patient with sporadic inclusion body myositis.Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection can lead to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), concomitantly with or without other inflammatory disorders such as myositis. These pathologies are considered immune-mediated diseases, and it is assumed that migration within tissues of both HTLV-1-infected CD4( ) T cells and anti-HTLV-1 cytotoxic T cells represents a pivotal event. However, although HTLV-1-infected T cells were found in inflamed lesions, the antigenic specificity of coinfiltrated CD8( ) T cells remains to be determined. In this study, we performed both ex vivo and in situ analyses using muscle biopsies obtained from an HTLV-1-infected patient with HAM/TSP and sporadic inclusion body myositis. We found that both HTLV-1-infected CD4( ) T cells and CD8( ) T cells directed to the dominant Tax antigen can be amplified from muscle cell cultures. Moreover, we were able to detect in two successive muscle biopsies both tax mRNA-positive mononuclear cells and T cells recognized by the Tax11-19/HLA-A*02 tetramer and positive for perforin. These findings provide the first direct demonstration that anti-Tax cytotoxic T cells are chronically recruited within inflamed tissues of an HTLV-1 infected patient, which validates the cytotoxic immune reaction model for the pathogenesis of HTLV-1-associated inflammatory disease.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
4/20. HTLV-I associated myelopathy (HAM) after blood transfusion in a patient with CD2 hairy cell leukemia.Hairy cell leukemia complicating hemolytic anemia developed in a 46-year-old woman. Morphologically and cytochemically typical hairy cells were found to express both CD20 and CD2 antigens. Expression of surface IgG of kappa-chain type and the rearrangement of Ig but not T-cell receptor beta genes confirmed a B-cell origin of the leukemia. blood transfusion was followed by disappearance of the hemolysis and a marked improvement of the leukemia. However, the patient developed progressive spastic spinal paraplegia about seven months after transfusion and was diagnosed as having HTLV-I associated myelopathy (HAM) by the demonstration of htlv-i antibodies in serum and cerebrospinal fluid. HTLV-I infection via the transfusion may have been involved in the hematologic improvement seen in this patient. autopsy showed demyelination, vacuolar degeneration, gliosis, and perivascular cuffing in the white matter of spinal cord without evidence of leukemic infiltration.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/20. Characterization of two human lymphoid cell lines producing human T-lymphotropic virus type I (HTLV-I) isolated from patients with HTLV-I-associated myelopathy or encephalopathy.Two cell lines, CNS-5 and CNS-6, were established by cocultivation of sedimented cells in cerebrospinal fluid (CSF) from two anti-human T-lymphotropic virus type I (HTLV-I) antibody-positive male patients with encephalopathy and HTLV-I-associated myelopathy, respectively, with peripheral blood mononuclear cells from a healthy seronegative female. These cell lines, possessing a normal female karyotype, revealed similar characteristics as follows; they expressed HTLV-I-related antigens, they produced C-type retrovirus particles, HTLV-I provirus genomes were integrated into their DNAs, and they had CD4 activated T-cell markers. In addition, immunocytochemical and immunoelectron microscopic studies showed peculiar immunoreactivity of these cell lines with anti-alpha/beta T-cell antigen receptor (TCR) antibodies; beta Fl, defining beta chain epitope, was only positive in the perinuclear spaces and rough endoplasmic reticulum in some cells, and WT31, recognizing alpha/beta framework, was mostly negative, while CD3 was expressed in the majority of the cells. These facts indicate that HTLV-I-infected cells were present in CSF of these two patients, and suggest that neurological disorders associated with HTLV-I may not be restricted to myelopathy and may include brain abnormalities.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
6/20. HTLV-I-associated myelopathy in a Californian: diagnosis by reactivity to a viral recombinant antigen.A male patient developed leg numbness and weakness, and bowel, bladder, and erectile dysfunction. Examination revealed an isolated thoracic myelopathy, with lower-extremity spasticity, decreased vibration and position sense, hyperreflexia, and Babinski's signs. serum and CSF showed antibody reactivity to human T-cell lymphotropic virus type I or II (HTLV-I/II), suggesting HTLV-I-associated myelopathy. Antibody reactivity to a unique HTLV-I recombinant protein provided definitive diagnosis of HTLV-I infection.- - - - - - - - - - ranking = 4keywords = antigen (Clic here for more details about this article) |
7/20. HTLV-I-associated myelopathy: clinicopathologic correlation with localization of provirus to spinal cord.A 49-year-old South African man developed a rapidly progressive myelopathy 14 months after blood transfusion and died 1 year after the onset of symptoms. Detailed pathologic examination of the spinal cord was consistent with the diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although no HTLV-I viral particles, antigens, or nucleic acids were detected in situ, polymerase chain reaction assays revealed HTLV-I proviral dna in cervical, thoracic, and lumbar levels of the spinal cord, with the greatest amount being detected at the thoracic level. These findings suggest that the pathogenesis of HAM/TSP depends on direct infection of neural or immune elements within the spinal cord.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
8/20. HTLV-I-associated myelopathy endemic in texas-born residents and isolation of virus from CSF cells.We report three texas-born patients with spastic paraparesis and well-documented infection with HTLV-I. CSF examination showed moderate pleocytosis, protein elevation, and elevated IgG index. oligoclonal bands were present in two patients. On MRI, one patient had frontal lobe lesions that were low intensity on T1- and high intensity on T2-weighted images. HTLV-I immunoblot studies of serum and CSF revealed reactivity to p19, p24, p53, gp46, or gp68 from all three patients. Titration studies of serum and CSF antibodies on ELISA and immunoblot assays indicated an intrathecal virus-specific response. HTLV-I-specific p19 antigen capture assay and polymerase chain reaction (PCR) demonstrated HTLV-I in lymphocyte cultures derived from each patient's peripheral blood mononuclear cells (PBMC) or CSF cells. Using HTLV-I- and HTLV-II-specific pol and gag primers, PCR studies of PBMC cells obtained directly from the patients demonstrated that the patients were infected with HTLV-I and not HTLV-II. These three cases are to our knowledge the only US cases in whom virus isolation from the CSF has been accomplished. Importantly, two patients may be the first US cases of myelopathy arising from endemic infection.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
9/20. Isolation and characterization of HTLV-I from symptomatic family members with tropical spastic paraparesis (HTLV-I encephalomyeloneuropathy).Human T lymphotropic virus type I (HTLV-I) was isolated from peripheral blood- and cerebrospinal fluid-derived mononuclear cells of a 13-y-old boy and from the peripheral blood lymphocytes of both his parents. All three had IgG antibodies to HTLV-I and varying degrees of the clinical features of tropical spastic paraparesis (TSP). The son also had IgM antibodies specific for HTLV-I in his serum. Isolations were successfully made from peripheral blood lymphocytes and cerebrospinal fluid lymphocytes stimulated with interleukin-2 or cocultivated with umbilical cord blood mononuclear cells. Established cell lines contained HTLV-I antigen by immunfluorescence and cell-associated virus by electron microscopy; cells became transformed in vitro as determined by their continuous growth in the absence of exogenous interleukin-2. This boy is the youngest TSP patient known to be reported, and the isolation of HTLV-I from all three family members suggests the causative role of this virus in TSP.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/20. Tropical spastic paraparesis: a model of virus-induced, cytotoxic T-cell-mediated demyelination?Tropical spastic paraparesis is a neurological disorder that is most commonly seen in certain tropical (mainly Caribbean) areas and that presents as a progressive spastic paraparesis and urinary dysfunction. Recent studies have revealed an association between tropical spastic paraparesis and human T-cell lymphotropic virus type I (HTLV-I) infection. We report the results of a detailed morphological and immunocytochemical study of a patient with tropical spastic paraparesis. Lesions were restricted to the spinal cord and optic nerve, where demyelination, inflammation, and fiber loss were common features. lymphocytes were seen closely applied to nerve fibers within which were changes resembling those seen in myelinated central nervous system cultures exposed to cytokines. Immunocytochemically, HTLV-I p19 core protein and a predominance of CD8 (suppressor/cytotoxic) T cells and expression of class I major histocompatibility antigen were demonstrated in spinal cord lesions. It is postulated that cytotoxic T cells, either directly or via cytokines, induce lysis of the myelin sheath and subsequently the axon, resulting in a mixed picture of demyelination and axonal loss with secondary tractal degeneration. Despite this destruction, extensive remyelination was evident within affected areas of spinal cord.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
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