RESUMO

BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) infection has been associated with recurrent and disseminated strongyloidiasis and adult T cell leukemia/lymphoma (ATLL). METHODS: We compared immunological aspects and markers for ATLL in HTLV-1 patients with or without strongyloidiasis, and evaluated the influence of Strongyloides stercoralis treatment on the immune response and clinical outcomes of HTLV-1 infection. RESULTS: Levels of TNFα and IFNγ were lower in patients coinfected with HTLV-1 and S. stercoralis than in patients with HTLV-1 only (p < 0.05), and there was an increase in TNFα levels after anthelmintic treatment. Levels of sIL-2R were higher in patients with HTLV-1 coinfected with S. stercoralis and anthelmintic treatment decreased sIL-2R levels (p < 0.05). The one patient who developed ATLL was coinfected with S. stercoralis. CONCLUSION: These data show that helminthic infection has a modulatory role in HTLV-1 infection and that S. stercoralis may be a cofactor in the development of ATLL.

Assuntos

Anti-Helmínticos/uso terapêutico , Infecções por HTLV-I/tratamento farmacológico , Receptores de Interleucina-2/sangue , Estrongiloidíase/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue , Adulto , Animais , Coinfecção , Progressão da Doença , Feminino , Infecções por HTLV-I/sangue , Infecções por HTLV-I/complicações , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Leucemia-Linfoma de Células T do Adulto/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-2/imunologia , Strongyloides stercoralis/imunologia , Estrongiloidíase/sangue , Estrongiloidíase/complicações , Estrongiloidíase/imunologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia

RESUMO

Human T cell lymphotropic virus type-1 (HTLV-1) induces activation and spontaneous proliferation of T cells with production of type-1 pro-inflammatory cytokines. It modifies the immune response to other antigens and increases susceptibility to infectious diseases. However, little is known about innate immunity in HTLV-1 infection. HTLV-1-infected individuals have higher spontaneous neutrophil activation than HTLV-1-seronegative individuals, as shown by the nitroblue tetrazolium (NBT) assay. This study was conducted to evaluate neutrophil function in HTLV-1-infected individuals. Participants in the study included 18 HTLV-1-infected individuals and 14 HTLV-1-seronegative controls. We evaluated the ability of neutrophils (PMNs) to control a parasite infection, to produce peroxynitrite, cytokines and chemokines and to express activation markers in cultures when stimulated with LPS or infected with Leishmania. When compared with the control group, there was no difference in the percentage of PMNs infected with Leishmania or in the number of amastigotes/100 PMNs in HTLV-1-infected individuals. The microbicidal activity of the PMNs and the levels of CXCL8 and CCL4 released by these cells did not show a difference between HTLV-1-infected individuals and the control group. In both the HTLV-1 group and the control group, infection with Leishmania or stimulation of PMNs led to cellular activation. These observations suggest that neutrophils from HTLV-1-infected individuals have preserved their ability to become activated and to produce chemokines and peroxynitrite after stimulation and that the susceptibility to infection by intracellular Leishmania amazonensis in HTLV-1-infected individuals does not depend on impairment of neutrophil function.

Assuntos

Quimiocinas/imunologia , Citocinas/imunologia , Infecções por HTLV-I/imunologia , Leishmania mexicana/imunologia , Neutrófilos/imunologia , Neutrófilos/parasitologia , Antígenos CD/biossíntese , Moléculas de Adesão Celular/biossíntese , Quimiocinas/biossíntese , Citocinas/biossíntese , Feminino , Proteínas Ligadas por GPI/biossíntese , Humanos , Imunidade Inata , Selectina L/biossíntese , Lipopolissacarídeos/imunologia , Masculino , Ativação de Neutrófilo , Neutrófilos/metabolismo , Ácido Peroxinitroso/biossíntese , Explosão Respiratória

RESUMO

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) is known to cause HTLV-associated myelopathy (HAM)/tropical spastic paraparesis and adult T cell leukemia. A growing body of evidence links HTLV-1 infection with an increasing spectrum of disease, including uveitis, periodontal disease, arthropathy, sicca syndrome, and neurologic deficits. OBJECTIVES: Despite recent findings, the natural history of HTLV-1 infection remains poorly defined. This study was designed to better characterize initial clinical and neurological findings in individuals diagnosed with HTLV-1 infection. STUDY DESIGN: We conducted a cross-sectional study of 71 individuals recently diagnosed with HTLV-1 and 71 uninfected age- and sex-matched blood donors in Salvador, Brazil. Subjects were administered a standardized questionnaire and underwent physical exam. RESULTS: HTLV-1 infected subjects were significantly more likely than controls to report complaints of hand and foot numbness (OR=5.3; 95% CI: 1.8-15.3; p=0.002 and OR=4.0; 95% CI: 1.3-12; p=0.013 respectively), difficulty running (OR=4.0; 95% CI: 1.1-14.2; p=0.032), nocturia (OR=5.0; 95% CI: 1.1-22.8; p=0.038), arthralgia (OR=3.3; 95% CI: 1.4-7.7; p=0.006), and photophobia (OR=3.3; 95% CI: 1.4-7.7; p=0.006). CONCLUSIONS: Neurologic, ocular and rheumatologic complaints may be the first manifestations of HTLV-1 infection. Therefore, all patients presenting with initial diagnosis should be rigorously screened for these symptoms.

Assuntos

Artropatia Neurogênica/etiologia , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Doenças Periodontais/etiologia , Síndrome de Sjogren/etiologia , Uveíte/etiologia , Adulto , Fatores Etários , Análise de Variância , Artropatia Neurogênica/diagnóstico , Artropatia Neurogênica/virologia , Brasil , Intervalos de Confiança , Estudos Transversais , Feminino , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/virologia , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/etiologia , Leucemia-Linfoma de Células T do Adulto/virologia , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/etiologia , Paraparesia Espástica Tropical/virologia , Doenças Periodontais/diagnóstico , Doenças Periodontais/virologia , Fatores Sexuais , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/virologia , Uveíte/diagnóstico , Uveíte/virologia

RESUMO

OBJECTIVES: To determine the prevalence of erectile dysfunction (ED) in human T-cell lymphotropic virus type I (HTLV-I)-infected patients, and its association with overactive bladder (OB). METHODS: In a cross-sectional study, 111 male patients with positive serology for HTLV-I (by enzyme-linked immunosorbent assay and Western blot) were examined between October 2003 and December 2006. Exclusion criteria were age <18 and >80 years, other neurological diseases, penile prosthesis, neoplasm, and psychological and mental disease. Patients were evaluated by a urologist and neurologist. ED was determined by application of the abridged form of 5-item International Index of Erectile Function (IIEF-5). ED was defined as IIEF-5 0 e 2). Diagnosis of HAM/TSP was performed according to World Health Organization recommendations. RESULTS: Of the total of 111 patients, 6 were excluded and 105 were analyzed. The mean age was 48 +/- 10.7 years. ED was observed in 55.2%. ED was documented in all patients who had HAM/TSP, in 79% of the group with EDSS > 0 and

Assuntos

Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Infecções por HTLV-I/complicações , Bexiga Urinária Hiperativa/complicações , Adulto , Idoso , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência

RESUMO

OBJECTIVE: Human T lymphotropic virus-type 1 (HTLV-1) activates the immune system leading to a persistent and exacerbated T-cell response with increased production of IFN-gamma and TNF-alpha. Overproduction of pro-inflammatory cytokines is correlated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although some HTLV-1 carriers also show high levels of these cytokines. In this study, the ability of regulatory cytokines and cytokine antagonists to inhibit spontaneous IFN-gamma production was investigated. METHOD: IFN-gamma levels were measured by ELISA before and after addition of cytokines or anti-cytokines. RESULTS: Addition of IL-10 significantly reduced spontaneous IFN-gamma synthesis in cell cultures from HTLV-1 carriers, while no differences were observed in HAM/TSP patients. There was also a tendency to decreased IFN-gamma levels in cell cultures from HTLV-1 carriers with exogenous addition of TGF-beta. In paired analysis, neutralization of IL-2 significantly decreased IFN-gamma production in HTLV-1 carriers but not in HAM/TSP patients. Neutralization of IL-15 was less effective than neutralization of IL-2 in modulating IFN-gamma production. In HTLV-1 carriers, anti-IL-2 and simultaneous addition of anti-IL-2 and anti-IL-15 decreased IFN-gamma synthesis by 46 and 64%, respectively, whereas in patients with HAM/TSP simultaneous neutralization of both anti-cytokines only decrease IFN-gamma levels by 27%. CONCLUSIONS: Although a large proportion of HTLV-1 carriers produced high levels of pro-inflammatory cytokines similar to those observed in HAM/TSP patients, immune response can be downregulated by cytokines or cytokine antagonists in most HTLV-1 carriers. This modulation can be an important step in the prevention of tissue damage and progression from the HTLV-1 carrier state to HAM/TSP.

Assuntos

Portador Sadio/imunologia , Interferon gama/biossíntese , Paraparesia Espástica Tropical/imunologia , Linfócitos T/imunologia , Idoso , Portador Sadio/metabolismo , Células Cultivadas , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , História do Século XVI , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Interferon gama/antagonistas & inibidores , Interleucina-10/metabolismo , Interleucina-15/antagonistas & inibidores , Interleucina-15/metabolismo , Interleucina-2/antagonistas & inibidores , Interleucina-2/imunologia , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/metabolismo , Linfócitos T/metabolismo , Fator de Crescimento Transformador beta/metabolismo

RESUMO

OBJECTIVE: To identify clinical and immunological markers associated with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHOD: 237 HTLV-I infected individuals were clinically assessed. They were classified according to the Expanded Disability Status Scale (EDSS) and Osames Motor Disability Score (OMDS). Cytokine levels were determined in HTLV-I seropositive individuals. RESULTS: 37 patients had HAM/TSP. There was a correlation between the degrees of disability assessed by both scales. There was also a correlation between the duration of HAM/TSP and the severity of disability assessed by either EDSS or OMDS. Higher levels of IFN-gamma were detected in unstimulated peripheral blood mononuclear cells (PBMC) from HAM/TSP patients as compared with HTLV-I carriers. CONCLUSION: This study shows the validity of the neurological scales to classify the degree of neurological disability in HTLV-I carriers and suggests a progressive behavior of HAM/TSP. This study also shows that IFN-gamma in PBMC supernatants are markers of HAM/TSP.

Assuntos

Citocinas/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Leucócitos Mononucleares/imunologia , Paraparesia Espástica Tropical/imunologia , Transtornos Psicomotores/diagnóstico , Adulto , Biomarcadores/análise , Avaliação da Deficiência , Feminino , Humanos , Masculino , Paraparesia Espástica Tropical/complicações , Transtornos Psicomotores/etiologia , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo

RESUMO

OBEJETIVO: Identificar marcadores clínicos e imunológicos associados com a mielopatia associada ao HTLV-I/paraparesia espástica tropical (MAH/PET). MÉTODO: 237 indivíduos infectados pelo HTLV-I foram clinicamente avaliados. Eles foram classificados de acordo com a escala expandida do estado de incapacidade de Kurtzke (EDSS) e escala de incapacidade motora de Osame (OMDS). Níveis de citocinas foram determinados nos indivíduos. RESULTADOS: 37 pacientes tinham MAH/PET. Houve correlação entre os graus de incapacidade pelas escalas. Houve também correlação entre a duração da MAH/PET e o grau da incapacidade pelas escalas. Níveis elevados de IFN-g foram detectados em células mononucleares de sangue periférico (CMSP) não estimuladas de pacientes com MAH/PET quando comparados com indivíduos HTLV-I positivos assintomáticos. CONCLUSÃO: Os dados demonstram a validade das escalas neurológicas para classificar o grau de incapacidade neurológica em portadores do HTLV-I e sugerem o comportamento progressivo da MAH/PET. Este estudo também demonstra que os níveis de IFN-g em sobrenadante de CMSP são marcadores da MAH/PET.

Assuntos

Adulto , Feminino , Humanos , Masculino , Citocinas/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Leucócitos Mononucleares/imunologia , Paraparesia Espástica Tropical/imunologia , Transtornos Psicomotores/diagnóstico , Biomarcadores/análise , Avaliação da Deficiência , Paraparesia Espástica Tropical/complicações , Transtornos Psicomotores/etiologia , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo

RESUMO

Human T cell lymphotropic virus type 1 (HTLV-1) infection is associated with an exacerbated type 1 immune response and secretion of high levels of proinflammatory cytokines. In contrast, helminthic infection induces a type 2 immune response. In the present study, the cytokine profile in HTLV-1 carriers coinfected with helminths (Strongyloides stercoralis and/or Schistosoma mansoni) was compared with that in HTLV-1 carriers not coinfected with helminths. Levels of interferon (IFN)- gamma were higher in HTLV-1 carriers not coinfected with helminths than in HTLV-1 carriers coinfected with helminths (P<.05). The overall frequency of IFN- gamma -expressing CD8+ and CD4+ cells was decreased in HTLV-1 carriers coinfected with helminths (P<.05). The percentage of interleukin (IL)-5- and IL-10-expressing T cells in HTLV-1 carriers coinfected with helminths was higher than that in HTLV-1 carriers not coinfected with helminths (P<.05). Moreover, we found that the prevalence of helminthic infection was 7-fold higher in HTLV-1 carriers than in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (P<.05). These data show that helminthic infection decreases activation of type 1 cells, which may influence the clinical outcome of HTLV-1 infection.

Assuntos

Portador Sadio/imunologia , Infecções por HTLV-I/complicações , Infecções por HTLV-I/imunologia , Helmintíase/complicações , Helmintíase/imunologia , Paraparesia Espástica Tropical/complicações , Adulto , Brasil , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Cultivadas , Feminino , Helmintíase/epidemiologia , Humanos , Interferon gama/análise , Interleucina-10/análise , Interleucina-5/análise , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/imunologia , Esquistossomose mansoni/complicações , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/imunologia , Estrongiloidíase/complicações , Estrongiloidíase/epidemiologia , Estrongiloidíase/imunologia , Carga Viral

RESUMO

Human T cell leukemia virus type-I (HTLV-I) infection is associated with spontaneous T cell activation and uncontrolled lymphocyte proliferation. An exacerbated type-1 immune response with production of pro-inflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) is significantly higher in patients with myelopathy associated to HTLV-I than in HTLV-I asymptomatic carriers. In contrast with HTLV-I, a chronic Schistosoma mansoni infection is associated with a type-2 immune response with high levels of interleukin (IL-4, IL-5, and IL-10) and low levels of IFN-gamma. In this study, clinical and immunological consequences of the HTLV-I and S. mansoni infection were evaluated. The immune response in patients with schistosomiasis co-infected with HTLV-I showed low levels of IL-5 (p < 0.05) in peripheral blood mononuclear cells cultures stimulated with S. mansoni antigen (SWAP) and decreased SWAP-specific IgE levels when compared with patients with only schistosomiasis (p < 0.05). Liver fibrosis was mild in all HTLV-I co-infected patients. Immunological response was also compared in individuals who had only HTLV-I infection with those who were co-infected with HTLV-I and helminths (S. mansoni and Strongyloides stercoralis). In patients HTLV-I positive co-infected with helminths the IFN-gamma levels were lower than in individuals who had only HTLV-I. Moreover, there were fewer cells expressing IFN-gamma and more cells expressing IL-10 in individuals co-infected with HTLV-I and helminths. These dates indicate that HTLV-I infection decrease type 2-response and IgE synthesis and are inversely associated with the development of liver fibrosis. Moreover, helminths may protect HTLV-I infected patients to produce large quantities of pro-inflammatory cytokines such as IFN-gamma.

Assuntos

Citocinas/biossíntese , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Cirrose Hepática/virologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/complicações , Animais , Antígenos de Helmintos/imunologia , Estudos de Casos e Controles , Doença Crônica , Infecções por HTLV-I/imunologia , Humanos , Imunidade Celular/imunologia , Leucócitos Mononucleares/imunologia , Cirrose Hepática/imunologia , Esquistossomose mansoni/imunologia , Estatísticas não Paramétricas

RESUMO

Human T cell leukemia virus type-I (HTLV-I) infection is associated with spontaneous T cell activation and uncontrolled lymphocyte proliferation. An exacerbated type-1 immune response with production of pro-inflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) is significantly higher in patients with myelopathy associated to HTLV-I than in HTLV-I asymptomatic carriers. In contrast with HTLV-I, a chronic Schistosoma mansoni infection is associated with a type-2 immune response with high levels of interleukin (IL-4, IL-5, and IL-10) and low levels of IFN-gamma. In this study, clinical and immunological consequences of the HTLV-I and S. mansoni infection were evaluated. The immune response in patients with schistosomiasis co-infected with HTLV-I showed low levels of IL-5 (p < 0.05) in peripheral blood mononuclear cells cultures stimulated with S. mansoni antigen (SWAP) and decreased SWAP-specific IgE levels when compared with patients with only schistosomiasis (p < 0.05). Liver fibrosis was mild in all HTLV-I co-infected patients. Immunological response was also compared in individuals who had only HTLV-I infection with those who were co-infected with HTLV-I and helminths (S. mansoni and Strongyloides stercoralis). In patients HTLV-I positive co-infected with helminths the IFN-gamma levels were lower than in individuals who had only HTLV-I. Moreover, there were fewer cells expressing IFN-gamma and more cells expressing IL-10 in individuals co-infected with HTLV-I and helminths. These dates indicate that HTLV-I infection decrease type 2-response and IgE synthesis and are inversely associated with the development of liver fibrosis. Moreover, helminths may protect HTLV-I infected patients to produce large quantities of pro-inflammatory cytokines such as IFN-gamma.

Assuntos

Humanos , Animais , Citocinas , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Cirrose Hepática , Schistosoma mansoni , Esquistossomose mansoni , Antígenos de Helmintos , Estudos de Casos e Controles , Doença Crônica , Imunidade Celular , Leucócitos Mononucleares

RESUMO

BACKGROUND: A small fraction of Human T cell Leukemia Virus type-1 (HTLV-I) infected subjects develop a severe form of myelopathy. It has been established that patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) show an exaggerated immune response when compared with the immunological response observed in HTLV-I asymptomatic carriers. In this study the immunological responses in HAM/TSP patients and in HTLV-I asymptomatic carriers were compared using several immunological assays to identify immunological markers associated with progression from infection to disease. METHODS: Immunoproliferation assays, cytokine levels of unstimulated cultures, and flow cytometry analysis were used to evaluate the studied groups. Nonparametric tests (Mann-Whitney U test and Wilcoxon matched-pairs signed ranks) were used to compare the difference between the groups. RESULTS: Although both groups showed great variability, HAM/TSP patients had higher spontaneous lymphoproliferation as well as higher IFN-gamma levels in unstimulated supernatants when compared with asymptomatic carriers. Flow cytometry studies demonstrated a high frequency of inflammatory cytokine (IFN-gamma and TNF-alpha) producing lymphocytes in HAM/TSP as compared to the asymptomatic group. This difference was accounted for mainly by an increase in CD8 cell production of these cytokines. Moreover, the HAM/TSP patients also expressed an increased frequency of CD28-/CD8+ T cells. Since forty percent of the asymptomatic carriers had spontaneous lymphoproliferation and IFN-gamma production similar to HAM/TSP patients, IFN-gamma levels were measured eight months after the first evaluation in some of these patients to observe if this was a transient or a persistent situation. No significant difference was observed between the means of IFN-gamma levels in the first and second evaluation. CONCLUSIONS: The finding that a large proportion of HTLV-I carriers present similar immunological responses to those observed in HAM/TSP, strongly argues for further studies to evaluate these parameters as markers of HAM/TSP progression.

Assuntos

Portador Sadio/imunologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano , Interferon gama/sangue , Paraparesia Espástica Tropical/imunologia , Adulto , Linfócitos T CD8-Positivos/imunologia , Portador Sadio/sangue , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/sangue , Humanos , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/sangue , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/metabolismo

RESUMO

Uma mulher de 28 anos soropositiva para HTLV-I, cursou com polaciúria, urgência miccional e urge incontinência como primeira manifestaçäo da infecçäo pelo vírus

Assuntos

Humanos , Feminino , Adulto , Infecções por HTLV-I/complicações , Infecções por HTLV-I/terapia , Bexiga Urinaria Neurogênica