RESUMEN
ABSTRACT Aim: To evaluate the efficacy of the onabotulinum toxin type A in the treatment of HTLV-1 associated overactive bladder and its impact on quality of life (QoL). Methods: Case series with 10 patients with overactive bladder refractory to conservative treatment with anticholinergic or physical therapy. They received 200Ui of onabotulinumtoxin type A intravesically and were evaluated by overactive bladder symptoms score (OABSS) and King's Health Questionnaire. Results: The mean (SD) of the age was 52 + 14.5 years and 60% were female. All of them had confirmed detrusor overactivity on urodynamic study. Seven patients had HAM/TSP. The median and range of the OABSS was 13 (12-15) before therapy and decreased to 1.0 (0-12) on day 30 and to 03 (0-14) on day 90 (p < 0.0001). There was a significant improvement in 8 of the 9 domains of the King's Health Questionnaire after the intervention. Hematuria, urinary retention and urinary infection were the complications observed in 3 out of 10 patients. The mean time to request retreatment was 465 days. Conclusion: Onabotulinum toxin type A intravesically reduced the OABSS with last long effect and improved the quality of life of HTLV-1 infected patients with severe overactive bladder.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Calidad de Vida , Infecciones por HTLV-I/complicaciones , Toxinas Botulínicas Tipo A/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Inhibidores de la Liberación de Acetilcolina/uso terapéutico , Fármacos Neuromusculares/uso terapéutico , Urodinámica , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/fisiopatología , Vejiga Urinaria Hiperactiva/virología , Evaluación de SíntomasRESUMEN
AIM: To evaluate the efficacy of the onabotulinum toxin type A in the treatment of HTLV-1 associated overactive bladder and its impact on quality of life (QoL). METHODS: Case series with 10 patients with overactive bladder refractory to conservative treatment with anticholinergic or physical therapy. They received 200Ui of onabotulinumtoxin type A intravesically and were evaluated by overactive bladder symptoms score (OABSS) and King's Health Questionnaire. RESULTS: The mean (SD) of the age was 52+14.5 years and 60% were female. All of them had confirmed detrusor overactivity on urodynamic study. Seven patients had HAM/TSP. The median and range of the OABSS was 13 (12-15) before therapy and decreased to 1.0 (0-12) on day 30 and to 03 (0-14) on day 90 (p<0.0001). There was a significant improvement in 8 of the 9 domains of the King's Health Questionnaire after the intervention. Hematuria, urinary retention and urinary infection were the complications observed in 3 out of 10 patients. The mean time to request retreatment was 465 days. CONCLUSION: Onabotulinum toxin type A intravesically reduced the OABSS with last long effect and improved the quality of life of HTLV-1 infected patients with severe overactive bladder.
Asunto(s)
Inhibidores de la Liberación de Acetilcolina/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Infecciones por HTLV-I/complicaciones , Fármacos Neuromusculares/uso terapéutico , Calidad de Vida , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Adulto , Anciano , Femenino , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Masculino , Evaluación de Síntomas , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/fisiopatología , Vejiga Urinaria Hiperactiva/virología , UrodinámicaRESUMEN
UNLABELLED: Human T cell lymphotropic virus type 1 (HTLV-1) is the causal agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While the immune response to HTLV-1 infection is polarized to the Th1-type, chronic helminth infections drive the Th2- and T regulatory-type, and are able to downregulate the inflammatory response in some autoimmune diseases. OBJECTIVE: To evaluate whether Schistosoma spp. antigens alter the in vitro cytokine response in HTLV-1 infection. METHODS: The recombinant Schistosoma antigens Sm29 and ShTSP2 (tetraspanin) and PIII, a fraction of the Schistosoma mansoni adult worm antigen were added to peripheral blood mononuclear cell (PBMC) cultures of HTLV-1-infected individuals and the levels of interferon (IFN)-γ and interleukin (IL)-10 in the supernatants were measured using the ELISA sandwich technique. RESULTS: Compared to the levels of cytokine in nonstimulated cultures, the levels of IFN-γ were reduced in 50, 47 and 50% of patients by the presence of Sm29, ShTsp2 and PIII, respectively. The downregulation of IFN-γ production in the presence of Sm29 antigen was observed mainly in subjects who had lower basal levels of this cytokine. The levels of IL-10, however, increased by the addition of the three antigens in the cultures in 74, 62 and 44% of individuals, respectively. In addition, there was a decrease in the ratio of IFN-γ/IL-10 levels in cultures stimulated with Sm29 and ShTSP2 when compared to nonstimulated ones. CONCLUSIONS: The Schistosoma spp. antigens used in this study were able to downmodulate IFN-γ production in vitro in HTLV-1 infection. This may be associated with the increased levels of IL-10 induced by the antigens.
Asunto(s)
Antígenos Helmínticos/inmunología , Infecciones por Deltaretrovirus/inmunología , Regulación hacia Abajo/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Schistosoma mansoni/inmunología , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Adulto , Animales , Antígenos Helmínticos/sangre , Células Cultivadas , Infecciones por Deltaretrovirus/sangre , Femenino , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Inflamación/sangre , Inflamación/inmunología , Inflamación/parasitología , Interferón gamma/antagonistas & inhibidores , Interferón gamma/biosíntesis , Interleucina-10/biosíntesis , Masculino , Persona de Mediana Edad , Neuroesquistosomiasis , Schistosoma mansoni/aislamiento & purificación , Linfocitos T Reguladores/parasitología , Células Th2/parasitología , Adulto JovenRESUMEN
The majority of patients infected with human T-cell lymphotropic virus-type 1 (HTLV-1) are considered carriers, but a high frequency of urinary symptoms of overactive bladder, common in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) have been documented in these patients. The aim of this study was to determine if immunological and viral factors that are seen in HAM/TSP are also observed in these patients. Participants were classified as HTLV-1 carriers (n = 45), HTLV-1 patients suffering from overactive bladder (n = 45) and HAM/TSP (n = 45). Cells from HTLV-1 overactive bladder patients produced spontaneously more proinflammatory cytokines than carriers. TNF-α and IL-17 levels were similar in HAM/TSP and HTLV-1 overactive bladder patients. High proviral load was found in patients with overactive bladder and HAM/TSP and correlated with proinflammatory cytokines. In contrast with findings in patients with HAM/TSP, serum levels of Th1 chemokines were similar in HTLV-1 overactive bladder and carriers. Exogenous addition of regulatory cytokines decreased spontaneous IFN-γ production in cell cultures from HTLV-1 overactive bladder patients. The results show that HTLV-1 overactive bladder and HAM/TSP patients have in common some immunological features as well as similar proviral load profile. The data show that HTLV-1 overactive bladder patients are still able to down regulate their inflammatory immune response. In addition, these patients express levels of chemokines similar to carriers, which may explain why they have yet to develop the same degree of spinal cord damage as seen in patients with HAM/TSP. These patients present symptoms of overactive bladder, which may be an early sign of HAM/TSP.
Asunto(s)
Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Vejiga Urinaria Hiperactiva/inmunología , Adulto , Anciano , Estudios Transversales , Citocinas/metabolismo , Femenino , Infecciones por HTLV-I/virología , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Provirus/aislamiento & purificación , Vejiga Urinaria Hiperactiva/virología , Carga ViralRESUMEN
BACKGROUND: Periodontal diseases (PDs) are infectious diseases in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. Recently, viruses have been implicated in the pathogenesis of PDs. Individuals infected with human T lymphotropic virus 1 (HTLV-1) present with abnormal oral health and a marked increased prevalence of periodontal disease. METHODS: In this study, we investigated the patterns of periodontopathogen infection and local inflammatory immune markers in HTLV-1-seropositive individuals with chronic periodontitis (CP/HTLV-1 group) compared with HTLV-1-seronegative individuals with chronic periodontitis (CP group) and periodontally healthy, HTLV-1-seronegative individuals (control group). RESULTS: Patients in the CP/HTLV-1 group had significantly higher values of bleeding on probing, mean probing depth, and attachment loss than patients in the CP group. The expression of tumor necrosis factor alpha and interleukin (IL) 4 was found to be similar in the CP and CP/HTLV-1 groups, whereas IL-12 and IL-17 levels trended toward a higher expression in the CP/HTLV-1 group. A significant increase was seen in the levels of IL-1beta and interferon gamma in the CP/HTLV-1 group compared with the CP group, whereas expression of the regulatory T cell marker FOXp3 and IL-10 was significantly decreased in the lesions from the CP/HTLV-1 group. Interestingly, similar frequency and/or load of periodontopathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans) and frequency of viruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus) characteristically associated with PDs were found in the CP/HTLV and CP groups. CONCLUSIONS: HTLV-1 may play a critical role in the pathogenesis of periodontal disease through the deregulation of the local cytokine network, resulting in an exacerbated response against a standard periodontopathogen infection.
Asunto(s)
Bacterias Anaerobias/aislamiento & purificación , Enfermedad Crónica , Citocinas/biosíntesis , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Periodontitis/microbiología , Adulto , Recuento de Colonia Microbiana , Femenino , Encía/patología , Herpesviridae/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Periodontitis/inmunología , Periodontitis/patología , Periodontitis/virologíaRESUMEN
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.
Asunto(s)
Citocinas/biosíntesis , Infecciones por HTLV-I/complicaciones , Virus Linfotrópico T Tipo 1 Humano/inmunología , Cirrosis Hepática/virología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/complicaciones , Animales , Antígenos Helmínticos/inmunología , Estudios de Casos y Controles , Enfermedad Crónica , Infecciones por HTLV-I/inmunología , Humanos , Inmunidad Celular/inmunología , Leucocitos Mononucleares/inmunología , Cirrosis Hepática/inmunología , Esquistosomiasis mansoni/inmunología , Estadísticas no ParamétricasRESUMEN
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.
Asunto(s)
Humanos , Animales , Citocinas , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Cirrosis Hepática , Schistosoma mansoni , Esquistosomiasis mansoni , Antígenos Helmínticos , Estudios de Casos y Controles , Enfermedad Crónica , Inmunidad Celular , Leucocitos MononuclearesRESUMEN
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.