RESUMO
INTRODUCTION: Previous studies have shown the existence of either cellular or humoral MBP-reactive elements up to 5 years after spinal cord injury (SCI), but not the presence of both after 10 years. MATERIALS AND METHODS: Twelve SCI patients, with more than 10 years of evolution, and 18 healthy blood donors were studied. Lymphocyte proliferation (colorimetric-BrdU ELISA assay) and antibody titers against MBP (ELISA Human IgG MBP-specific assay) were assessed. RESULTS: SCI patients presented a significant T-cell proliferation against MBP (lymphocyte proliferation index: 3.7 ± 1.5, mean ± SD) compared to control individuals (0.7 ± 0.3; P < 0.001). Humoral response analysis yielded a significant difference (P < 0.0001) between the antibody titers of controls and SCI patients. A significant correlation between cellular and humoral responses was observed. Finally, patients with an ASIA B presented the highest immune responses. CONCLUSION: This work demonstrates, for the first time, the existence of both cellular and humoral responses against MBP in the chronic stages (>10 years) of injury.
Assuntos
Imunidade Humoral/imunologia , Proteína Básica da Mielina/imunologia , Paraplegia/imunologia , Traumatismos da Medula Espinal/imunologia , Adulto , Anticorpos/sangue , Estudos de Casos e Controles , Proliferação de Células , Doença Crônica , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Paraplegia/sangue , Paraplegia/etiologia , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/complicações , Linfócitos T/patologia , Fatores de TempoRESUMO
Bovine paraplegic syndrome (BPS) is a debilitating cattle disease of unknown origin that is characterized by leukocytosis, lymphocytopenia and monocytopenia. The major clinical signs are difficulties in locomotion affecting hind limbs, hypoalgesia in the hind quarters, posterior paralysis and death within 72 to 96 hours after recumbency. To investigate the aetiological basis of BPS, we examined a possible association of the syndrome with infection by bovine immunodeficiency virus (BIV), a lentivirus implicated in immune system dysfunction and central nervous system lesions in cattle. Serum samples (n = 1,278) were collected from both healthy and BPS-prevalent cattle herds in Venezuela, and organ extracts were prepared from euthanized animals (n = 11) suspected of having BPS. Sera were analysed for reactivity to recombinant BIV and bovine leukaemia virus gag precursor proteins by immunoblot procedures. Serum reactivity to BIV ranged from 12 to 66% between groups of BPS prevalent herds. The percentage of samples reactive to BLV antigen was much lower (2 to 17%). Rabbits inoculated with extracts from BPS-afflicted animals exhibited an anamnestic immune response to BIV antigens as well as the presence of BIV gag antigens in their tissues. We present evidence for a possible association between BPS disease and a viral agent related to BIV. The role of BIV, in combination with malnutrition, in BPS is discussed.
Assuntos
Doenças dos Bovinos/virologia , Vírus da Imunodeficiência Bovina/fisiologia , Infecções por Lentivirus/veterinária , Paraplegia/veterinária , Animais , Anticorpos Antivirais/sangue , Bovinos , Doenças dos Bovinos/imunologia , Linhagem Celular , Vírus da Imunodeficiência Bovina/imunologia , Vírus da Imunodeficiência Bovina/isolamento & purificação , Infecções por Lentivirus/sangue , Infecções por Lentivirus/complicações , Infecções por Lentivirus/imunologia , Vírus da Leucemia Bovina/imunologia , Paraplegia/sangue , Paraplegia/imunologia , Paraplegia/virologia , Coelhos , Síndrome , VenezuelaRESUMO
Recent neuroepidemiological studies of endemic tropical spastic paraparesis (TSP) have confirmed the existence of high-prevalence foci in several tropical islands, including Jamaica and Martinique in the Caribbean, Tumaco off the Pacific coast of Colombia, and the Seychelles in the Indian Ocean. There is a net preponderance of TSP in persons of Black African ancestry, although Caucasian, Hindu, Amerindian, and Orientals have been affected. The epidemiological, clinical, laboratory, and neuropathological features of TSP are reviewed here, as well as the evidence in favor of its retroviral origin.
Assuntos
Paraplegia/epidemiologia , Adolescente , Adulto , Fatores Etários , Anticorpos Antivirais/análise , Sistema Nervoso Central/patologia , Colômbia , Anticorpos Antideltaretrovirus , Infecções por Deltaretrovirus/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/epidemiologia , Espasticidade Muscular/genética , Espasticidade Muscular/imunologia , Espasticidade Muscular/patologia , Paraplegia/genética , Paraplegia/imunologia , Paraplegia/patologia , Grupos Raciais , Fatores Sexuais , Seicheles , Doenças da Medula Espinal/complicações , Clima Tropical , Índias OcidentaisRESUMO
We report clinical and laboratory investigations of 47 native-born Jamaican patients with endemic tropical spastic paraparesis and of 1 patient with tropical ataxic neuropathy. Mean age at onset was 40 years, with a female-male preponderance (2.7:1). Neurological features of endemic tropical spastic paraparesis are predominantly those of a spastic paraparesis with variable degrees of proprioceptive and/or superficial sensory impairment. Using enzyme-linked immunoabsorbent assay (ELISA), IgG antibodies to human T-lymphotropic virus type I (HTLV-I) were present in 82% of sera and 77% of cerebrospinal fluids. On Western blot analysis, IgG antibodies detected the p19 and p24 gag-encoded core proteins in both serum and cerebrospinal fluid. Titers were tenfold higher by ELISA in serum than in cerebrospinal fluid, and some oligoclonal bands present in fluid were not seen in serum. Serum-cerebrospinal fluid albumin ratios were normal, and IgG indexes indicated intrathecal IgG synthesis. Histopathological changes showed a chronic inflammatory reaction with mononuclear cell infiltration, perivascular cuffing, and demyelination that was predominant in the lateral columns. In 1 patient, a retrovirus morphologically similar to HTLV-I on electron microscopy was isolated from spinal fluid. Our investigations show that endemic tropical spastic paraparesis in Jamaica is a retrovirus-associated myelopathy and that HTLV-I or an antigenically similar retrovirus is the causal agent.
Assuntos
Infecções por Deltaretrovirus/complicações , Paraplegia/etiologia , Medicina Tropical , Adolescente , Adulto , Idoso , Anticorpos Anti-Idiotípicos/análise , Anticorpos Antivirais/análise , Deltaretrovirus/isolamento & purificação , Anticorpos Antideltaretrovirus , Feminino , Humanos , Imunoglobulina G/imunologia , Jamaica , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/líquido cefalorraquidiano , Espasticidade Muscular/etiologia , Espasticidade Muscular/imunologia , Paraplegia/líquido cefalorraquidiano , Paraplegia/imunologiaRESUMO
A high-incidence focus of tropical spastic paraparesis (TSP) occurs on the South Pacific coast of Colombia. Of 55 patients studied, 52 (94.5%) had IgG antibodies to the human T-cell lymphotropic virus type I (HTLV-I) in serum and/or cerebrospinal fluid. Control groups did not show similar high positivity. Our results suggest that HTLV-I or other antigenically related retroviruses may be the cause of TSP in Colombia. Similar clinical, laboratory, and epidemiological findings have been reported in widely remote geographical regions of the world, with very similar clinical pictures of TSP in all high-incidence regions. The demonstration of IgG antibodies in serum and cerebrospinal fluid of patients with TSP in the Caribbean and Seychelles Islands, southern Japan, and the Ivory Coast indicate that the HTLV-I retrovirus could be the cause of this "tropical" myeloneuropathy.
Assuntos
Anticorpos Antivirais/análise , Paraplegia/epidemiologia , Medicina Tropical , Adolescente , Adulto , Anticorpos Anti-Idiotípicos/análise , Anticorpos Anti-Idiotípicos/líquido cefalorraquidiano , Anticorpos Antivirais/síntese química , Colômbia , Anticorpos Antideltaretrovirus , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/imunologia , Imunoglobulinas/análise , Imunoglobulinas/líquido cefalorraquidiano , Focalização Isoelétrica , Masculino , Espasticidade Muscular/líquido cefalorraquidiano , Espasticidade Muscular/epidemiologia , Espasticidade Muscular/imunologia , Bandas Oligoclonais , Paraplegia/líquido cefalorraquidiano , Paraplegia/imunologiaRESUMO
Human T-lymphotropic virus type I (HTLV-I)-associated tropical spastic paraparesis in Martinique has been identified in 54 patients, 49 women and 5 men. This myelopathy represents an endemic problem on this island and the earliest documented case dates from 1952. A blood transfusion history was obtained in 7 of the 54 patients (13%). There was a preponderance of cases from the northern Atlantic coast of Martinique, the most humid region on the island. The prevalence in this region reached 49.5 per 100,000, compared with the global prevalence of 11.9 cases per 100,000 for the island. An immune-mediated mechanism may be important in the pathogenesis of HTLV-I-associated tropical spastic paraparesis.
Assuntos
Anticorpos Antivirais/análise , Paraplegia/epidemiologia , Medicina Tropical , Adulto , Reações Antígeno-Anticorpo , Células Sanguíneas/patologia , Doadores de Sangue , Procedimentos Cirúrgicos Cardíacos , Líquido Cefalorraquidiano/citologia , Anticorpos Antideltaretrovirus , Feminino , Humanos , Linfócitos/patologia , Masculino , Martinica , Espasticidade Muscular/epidemiologia , Espasticidade Muscular/etiologia , Espasticidade Muscular/imunologia , Espasticidade Muscular/transmissão , Paraplegia/etiologia , Paraplegia/imunologia , Paraplegia/transmissão , Reação TransfusionalRESUMO
Two patients from Martinique with tropical spastic paraparesis had antibodies to human T-lymphotropic virus type I (HTLV-I) in serum and spinal fluid but no antibodies to other retroviruses tested. They presented with spastic weakness of both lower extremities, hyperreflexia with upgoing toes, sphincteric dysfunction, and normal sensation. By means of agarose isoelectric focusing and selective immunoblotting we demonstrated an increased intrathecal synthesis of IgG antibodies to HTLV-I in the spinal fluid. Unique oligoclonal bands of IgG antibodies to HTLV-I were present in the cerebrospinal fluid. Using a battery of monoclonal antibodies we also found in these patients an increased number of circulating T cells that expressed activation markers. We conclude that the HTLV-I retrovirus associated with tropical spastic paraparesis has both lymphocytotropic and neurotropic properties.
Assuntos
Paraplegia/imunologia , Medicina Tropical , Adulto , Anticorpos Anti-Idiotípicos/análise , Anticorpos Anti-Idiotípicos/líquido cefalorraquidiano , Anticorpos Antivirais/análise , Anticorpos Antivirais/líquido cefalorraquidiano , Anticorpos Antideltaretrovirus , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulinas/análise , Imunoglobulinas/líquido cefalorraquidiano , Linfócitos/classificação , Imageamento por Ressonância Magnética , Martinica , Pessoa de Meia-Idade , Espasticidade Muscular/complicações , Espasticidade Muscular/imunologia , Espasticidade Muscular/microbiologia , Espasticidade Muscular/patologia , Bandas Oligoclonais , Paraplegia/complicações , Paraplegia/microbiologia , Paraplegia/patologiaRESUMO
Three of 6 patients with spastic paraparesis in Lima, Peru, were found to have antibodies to human T-lymphotropic virus type I (HTLV-I). Blood and cerebrospinal fluid antibodies were confirmed by Western blot analysis. Multilobulated lymphocytes in blood and cerebrospinal fluid of the index case stained with monoclonal antibodies for T-helper cells and for T10, an activation marker. Blood mononuclear cells from patients with HTLV-I-associated myelopathy showed spontaneous proliferation in culture, evidence of interleukin-2 receptors, and decreased natural killer cell activity.
Assuntos
Infecções por Deltaretrovirus , Paraplegia/etiologia , Adulto , Idoso , Anticorpos Antivirais/análise , Anticorpos Antivirais/líquido cefalorraquidiano , Células Sanguíneas/patologia , Divisão Celular , Anticorpos Antideltaretrovirus , Infecções por Deltaretrovirus/líquido cefalorraquidiano , Infecções por Deltaretrovirus/imunologia , Infecções por Deltaretrovirus/patologia , Feminino , Humanos , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/líquido cefalorraquidiano , Espasticidade Muscular/etiologia , Espasticidade Muscular/imunologia , Espasticidade Muscular/patologia , Mielite/etiologia , Paraplegia/líquido cefalorraquidiano , Paraplegia/imunologia , Paraplegia/patologia , Peru , Linfócitos T/classificaçãoRESUMO
The neuropathological examination of the spinal cord of 2 Jamaican patients with classical tropical spastic paraparesis disclosed an intense chronic meningomyelitis with demyelination. In the 1 case in which serum and cerebrospinal fluid were available, antibodies to the human T-lymphotropic virus type 1 were found.
Assuntos
Paraplegia/patologia , Medicina Tropical , Adulto , Anticorpos Anti-Idiotípicos/análise , Anticorpos Anti-Idiotípicos/líquido cefalorraquidiano , Anticorpos Antivirais/análise , Anticorpos Antivirais/líquido cefalorraquidiano , Encéfalo/patologia , Anticorpos Antideltaretrovirus , Feminino , Humanos , Imunoglobulina G/imunologia , Jamaica , Espasticidade Muscular/imunologia , Espasticidade Muscular/patologia , Paraplegia/imunologia , Medula Espinal/patologiaRESUMO
The clinical syndrome earlier designated as paraparesia espástica del Pacífico is an isolated form of tropical spastic paraparesis (TSP) that was reported in 1981 in the southern Pacific lowlands of Columbia in and near Tumaco. The clinical features are similar to those of TSP reported in Jamaica, Martinique, the Seychelles, and the Ivory Coast of Africa and resemble also those clinical features of the human T-lymphotropic virus type I (HTLV-I)-associated myelopathy described in southern Japan. Since HTLV-I infection is closely associated with TSP, we conducted a case-control study to evaluate the role of HTLV-I-associated risk factors among patients from the endemic focus in Tumaco, Colombia, and the seroprevalence rates of this virus in other geographical areas of the Pacific Colombian lowlands with and without TSP. From our seroprevalence study of antibodies to HTLV-I among TSP index patients, matched controls, household contacts (first- and second-degree relatives), and healthy controls from these areas, we found a strong association between HTLV-I and TSP. Also, there is a high seroprevalence of HTLV-I among sexual partners of patients and to a lesser extent among their offspring and other relatives some of whom had an early mean acquisition of antibodies to HTLV-I. Heterosexual promiscuity and other close interpersonal contact may play an important role in the transmission of TSP in the Pacific lowlands of Colombia.