Polymorphism in the interleukin-10 gene is associated with overactive bladder phenotype associated with HTLV-1 infection

Abstract INTRODUCTION Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. METHODS We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. RESULTS No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). CONCLUSIONS Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.

The relationship between atopy and neurological manifestations in HTLV-1 infection

Abstract INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1)induces exaggerated Th1 responses, whereas atopy is associated with exacerbated Th2 responses. METHODS: Here, a cross-sectional study compared the prevalence of atopy in HTLV-1 carriers and HAM/TSP patients. It also compared the spontaneous cytokine production in HTLV-1-infected individuals. A retrospective cohort study evaluated the development of neurological manifestations in atopic and non-atopic carriers. RESULTS: Atopic HAM/TSP patients with high IFN-γ production exhibited higher IL-5 levels than non-atopic patients. Allergic rhinitis accelerated the development of Babinski signals and overactive bladders. CONCLUSIONS: Abnormal Th1 and Th2 responses coexist in HTLV-1-infected individuals and allergic diseases may worsen the clinical course of HTLV-1 infections.

Onabotulinumtoxin type A improves lower urinary tract symptoms and quality of life in patients with human T cell lymphotropic virus type 1 associated overactive bladder

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.

Immunopathogenesis and neurological manifestations associated to HTLV-1 infection / Imunopatogênese e manifestações neurológicas associadas à infecção pelo HTLV-1

The human T lymphotropic virus type-1 (HTLV-1) was the first human retrovirus identified. The virus is transmitted through sexual intercourse, blood transfusion, sharing of contaminated needles or syringes and from mother to child, mainly through breastfeeding. In addition to the well-known association between HTLV-1 and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), several diseases and neurologic manifestations have been associated with the virus. This review was conducted through a PubMed search of the terms HTLV-1, immune response and neurological diseases. Emphasis was given to the most recent data regarding pathogenesis and clinical manifestations of HTLV-1 infection. The aim of the review is to analyze the immune response and the variety of neurological manifestations associated to HTLV-1 infection. A total of 102 articles were reviewed. The literature shows that a large percentage of HTLV-1 infected individuals have others neurological symptoms than HAM/TSP. Increased understanding of these numerous others clinical manifestations associated to the virus than adult T cell leukemia/lymphoma (ATLL) and HAM/TSP has challenged the view that HTLV-1 is a low morbidity infection.

O vírus linfotrópico de células T humanas do tipo 1 (HTLV-1) foi o primeiro retrovírus humano identificado. O vírus é transmitido via relação sexual, transfusão de sangue, compartilhamento de agulhas ou seringas contaminadas ou da mãe para o filho, principalmente através da amamentação. Além da conhecida associação entre o HTLV-1 e a mielopatia associada ao HTLV-1 (HAM/TSP), várias doenças e manifestações neurológicas tem sido associadas com o vírus. Esta revisão de literatura foi conduzida através de pesquisa ao banco de dados do PubMed, com os termos HTLV-1, resposta imune e doenças neurológicas. Foram enfatizados os dados mais recentes sobre a patogênese e às manifestações clínicas na infecção pelo HTLV-1. O objetivo dessa revisão é analisar a resposta imune e a variedade de manifestações neurológicas associadas com a infecção pelo HTLV-1. Um total de 102 artigos foi analisado. A literatura mostra que grande porcentagem de indivíduos infectados pelo HTLV-1 apresenta sintomas neurológicos mesmo na ausência de HAM/TSP. Uma maior compreensão das várias manifestações clínicas associadas ao vírus, além da leucemia/linfoma de células T do adulto (ATLL) e HAM/TSP, auxilia a estabelecer que, na realidade, a infecção pelo vírus possui uma morbidade maior do que se pensava.

Association of cytokines, neurological disability, and disease duration in HAM/TSP patients

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.

Spontaneous neutrophil activation in HTLV-1 infected patients

Human T cell lymphotropic Virus type-1 (HTLV-1) induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT) to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy); 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS)-stimulated neutrophil activity (reduction of NBT to formazan). The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001) in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24 percent and 17±4.8 percent respectively (p< 0.001), while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20 percent). Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

Clinical and immunological consequences of human T cell leukemia virus type-I and Schistosoma mansoni co-infection

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.