RESUMEN
Human T-lymphocytic virus 1 (HTLV-1) is mainly associated with adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP exhibit significant changes in their immune response, and HTLV-1 infection can interfere in cytokine production and perhaps in T cell production. The aims of this study were to evaluate thymic function in HAM/TSP patients and HTLV-1 healthy carriers (HCs) and correlate it to age and interleukin 7 (IL-7) gene expression. Thymic function in 21 HAM/TSP patients and 12 HCs was evaluated by quantifying T cell receptor rearrangement excision circle (TREC) particles and IL-7 gene expression, both measured by quantitative polymerase chain reaction. HAM/TSP patients presented lower TREC particle counts (p = 0.0112) and lower IL-7 expression (p = 0.0102) than HCs. Both TREC particles and IL-7 gene expression were separately analyzed in two age groups: ≤ 59 years and ≥60 years, The ≤59-year-old HAM/TSP patients had a lower TREC count compared with the ≤59-year-old HCs (p = 0.0476). In conclusion, HAM/TSP development could interfere with thymic function because the results showed TREC particle reduction in HAM/TSP patients in relation to HCs, and it could be associated with a concomitant reduction in IL-7 expression.
Asunto(s)
Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/fisiología , Paraparesia Espástica Tropical/inmunología , Linfocitos T/inmunología , Timo/inmunología , Adolescente , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Regulación de la Expresión Génica , Humanos , Interleucina-7/metabolismo , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T/genética , Adulto JovenRESUMEN
This was a cross-sectional prospective study. We performed a multivariate statistical analysis of the neurological signs and symptoms of patients infected with human T cell lymphotropic virus type 1 (HTLV-1) in an attempt to separate them into distinct groups and identify clinical-neurological manifestations that could differentiate the various profiles. The study was performed in the city of Belém (state of Pará), located in the Amazon region of Brazil, from 2014 to 2016. We determined muscle strength and tone, reflexes, sensations, sphincter function, gait, and the Expanded Disability Status Scale score among individuals with HTLV-I. We then used exploratory statistical methods in an attempt to find different profiles and establish distinct groups. We analyzed 60 patients with HTLV-1. The filtering of the data, performed with mixed PCA, gave rise to a streamlined database with the most informative data and suggested the formation of three statistically distinct groups: asymptomatic carriers (AC), mono/oligosymptomatic (MOS), and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSPd), AC and MOS (p = 0.002), AC and HAM/TSPd (p < 0.001), and HAM/TSPd and MOS (p = 0.001). The subsequent cluster analysis confirmed the formation of three clusters. The classification and regression tree demonstrated that altered gait was the most important variable for the classification of an individual with HAM/TSPd and that, in the absence of this impairment, hyperreflexia characterized MOS. The present study was able to separate patients infected by HTLV-1 into three clinical groups (AC, HAM/TSPd, and MOS) and identify clinical manifestations that could differentiate the various patient groups.
Asunto(s)
Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/fisiopatología , Reflejo Anormal , Adulto , Enfermedades Asintomáticas , Análisis por Conglomerados , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Marcha/fisiología , Virus Linfotrópico T Tipo 1 Humano/fisiología , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Paraparesia Espástica Tropical/clasificación , Paraparesia Espástica Tropical/virología , Análisis de Componente Principal , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0186055.].
RESUMEN
Hypomyopathic dermatomyositis (HDM) is a rare form of dermatomyositis (DM). Interstitial lung disease (ILD) associated with clinically amyopathic DM (CADM-ILD) or hypomyopathic DM (HDM-ILD) is a rare condition with a more unfavorable prognosis than ILD associated with classic DM (CDM-ILD). There is no effective treatment for HDM-ILD. A 62-year-old woman with a 6-month history of chronic polyarthritis and myalgia presented skin lesions characteristic of DM (erythematous lesion on extensor surface of elbows, Gottron's papules, V-neck sign) with no clinical muscle impairment (global muscle strength: grade 5). Muscle enzymes (creatine kinase, lactic dehydrogenase, and aldolase) and electroneuromyography (ENMG) were normal. Computed tomography of the chest revealed ILD. Magnetic resonance imaging and muscle biopsy revealed subclinical muscle impairment. High doses of corticosteroids were used without success. As an alternative, 1500 mg/day of mycophenolate mofetil (MMF) was combined with low doses of prednisone, and the patient demonstrated a good clinical response after 3 months of this combination. Twenty-five months after initiating treatment, ILD remains in remission with the use of MMF and a low dose of prednisone. Therefore, MMF can be a good option for the treatment of HDM-ILD.
Asunto(s)
Antiinflamatorios/uso terapéutico , Dermatomiositis/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Ácido Micofenólico/uso terapéutico , Dermatomiositis/complicaciones , Quimioterapia Combinada , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Persona de Mediana Edad , Prednisona/uso terapéutico , Resultado del TratamientoRESUMEN
HTLV-1 infects principally CD4+ T cells that are the main reservoirs of the virus in vivo, which play an important role in the immunological response. Most of the infected patients are asymptomatic. However, 2-3% of patients will develop HAM/TSP or Adult T lymphoma. HAM/TSP is a chronic inflammatory disease of the central nervous system, which is characterized by unremitting myelopathic symptoms. Studies have shown that cytokines levels alterations (IFN-γ and TNF-α) were associated with tissue injury in HAM/TSP. The aims of this study were to compare the gene expression of IFN-γ, IL-4 and IL-10 of asymptomatic and HAM/TSP HTLV-1 infected patients, and to correlate the gene expression with those of clinical symptoms. 28 subjects were included, 20 asymptomatic HTLV-1 and 8 with HAM/TSP. Spasticity was evaluated using the Modified Ashworth Scale and the degree of walking aid was classified on a progressive scale. The relative gene expression of IFN-γ, IL-4, and IL-10 was measured by Real-Time PCR. Results showed high gene expression of IFN-γ for all patients, but it was higher among HAM/TSP. A significant correlation was observed between IFN-γ gene expression and the degree of walking aid, and IFN-γ gene expression was higher among wheelchair users compared to non-wheelchair users. No association was found with IL-4 and IL-10. These findings indicate that HAM/TSP patients express higher amounts of IFN-γ than asymptomatic patients, and more importantly, the expression of this cytokine was strongly correlated with the need of walking aid.
Asunto(s)
Virus Linfotrópico T Tipo 1 Humano/inmunología , Inmunidad , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/etiología , Adulto , Anciano , Citocinas/genética , Citocinas/metabolismo , Progresión de la Enfermedad , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Only a limited percentage of infected individuals develop disease in response to the virus while the majority remain asymptomatic, and HAM/TSP is the most common clinical manifestation of the virus. HAM/TSP is an inflammatory disease of the central nervous system (CNS); however, the mechanism by which HTLV-1 induces HAM/TSP is not yet clear. CD4(+) T lymphocytes are the main reservoirs of HTLV-1 in vivo and perform an important role in the immunological response to this retrovirus. This virus-host interaction may provoke changes in the immunological response, such as the enhanced production of inflammatory cytokines and the spontaneous proliferation of T CD4(+) lymphocytes, which are implicated in the pathogenesis of HAM/TSP.