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Disseminated leishmaniasis (DL) caused by L. braziliensis is characterized by the presence of 10 to more than 1000 lesions spread on the body. While protection against Leishmania is mediated by macrophages upon activation by IFN-γ produced by CD4+T cells, the pathology of disseminated leishmaniasis (DL) could be mediated by macrophages, NK, and CD8+T cells. Herein, we evaluate the participation of senescent CD8+T cells in the pathogenesis of DL. Methods: Peripheral blood mononuclear cells (PBMCs), biopsies, co-cultures of CD8+T cells with uninfected and infected macrophages (MØ), and PBMC cultures stimulated with soluble L. braziliensis antigen (SLA) for 72 h from patients with cutaneous leishmaniasis (CL) and DL were used to characterize senescent CD8+T cells. Statistical analysis was performed using the Mann-Whitney and Kruskal-Wallis tests, followed by Dunn's. Results: Patients with DL have an increase in the frequency of circulating CD8+T cells that present a memory/senescent phenotype, while lesions from DL patients have an increase in the frequency of infiltrating CD8+T cells with a senescent/degranulation phenotype. In addition, after specific stimuli, DL patients' circulating CD8+T with memory/senescent profile, showing degranulation characteristics, increased upon SLA stimuli, and those specific CD8+T cells from DL patients had an increased degranulation phenotype, causing more apoptosis of infected target cells. Conclusions: DL patients show a higher frequency of cytotoxic senescent CD8+T cells compared to CL patients, and that could promote the lysis of infected cells, although without parasite killing, releasing Leishmania to the extracellular compartment, contributing to the spread of parasites.

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BACKGROUND: Joint pain in the absence or with little synovitis is observed in a large percentage of HTLV-1 infected subjects. As the virus infect CD4 + and CD8 + positive, macrophages and B cells an exaggerated production of pro-inflammatory cytokines is detected in these patients. However, the possible association of HTLV-1 infection with autoimmune diseases has not been documented definitively and the clinical characteristics of HTLV-1 associated arthropathy has not been defined. The objective this study is to describe clinic and radiographic features in HTLV-1-infected individuals with complaints of joint pain. METHODS: Cross-sectional study enrolling HTLV-1-infected individuals with chronic joint pain, aged up to 75 years, both genders and seronegative controls with osteoarthritis. All participants underwent conventional radiography of the hips, knees and ankles. RESULTS: Eighty-one HTLV-1 infected patients and 30 subjects with osteoarthritis participated in the study. Polyarticular and symmetrical arthritis prevailed in the HTLV-1 positive group (54%), while oligoarticular and asymmetrical (44%) were more common in controls (p < 0.05). The frequency of enthesophytes (90%) in HTLV-1-infected patients was greater than in the control group (73%) (p < 0.05). Radiographic features were similar in HTLV-1 carriers and in patients with probable or definite HTLV-1 associated myelopathy. The presence of enthesophytes in the absence of joint space reduction or osteophytes was only observed in HTLV-1-infected individuals (p < 0.001). Magnetic resonance imaging of the ankles of five HTLV-1-infected patients and five controls demonstrated a higher frequency of enthesitis, bursitis and osteitis in the HTLV-1 infected group. CONCLUSION: HTLV-1-associated arthropathy is clinically characterized by symmetrical polyarthralgia and the main radiological finding is the presence of enthesophytes in the absence of osteophytes and joint space narrowing.

Assuntos

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Abstract Background: Joint pain in the absence or with little synovitis is observed in a large percentage of HTLV-1 infected subjects. As the virus infect CD4 +and CD8 +positive, macrophages and B cells an exaggerated production of pro-inflammatory cytokines is detected in these patients. However, the possible association of HTLV-1 infection with autoimmune diseases has not been documented definitively and the clinical characteristics of HTLV-1 associated arthropathy has not been defined. The objective this study is to describe clinic and radiographic features in HTLV-1-infected individuals with complaints of joint pain. Methods: Cross-sectional study enrolling HTLV-1-infected individuals with chronic joint pain, aged up to 75 years, both genders and seronegative controls with osteoarthritis. All participants underwent conventional radiography of the hips, knees and ankles. Results: Eighty-one HTLV-1 infected patients and 30 subjects with osteoarthritis participated in the study. Polyarticular and symmetrical arthritis prevailed in the HTLV-1 positive group (54%), while oligoarticular and asymmetrical (44%) were more common in controls ( p < 0.05). The frequency of enthesophytes (90%) in HTLV-1-infected patients was greater than in the control group (73%) ( p < 0.05). Radiographic features were similar in HTLV-1 carriers and in patients with probable or definite HTLV-1 associated myelopathy. The presence of enthesophytes in the absence of joint space reduction or osteophytes was only observed in HTLV-1-infected individuals ( p < 0.001). Magnetic resonance imaging of the ankles of five HTLV-1-infected patients and five controls demonstrated a higher frequency of enthesitis, bursitis and osteitis in the HTLV-1 infected group. Conclusion: HTLV-1-associated arthropathy is clinically characterized by symmetrical polyarthralgia and the main radiological finding is the presence of enthesophytes in the absence of osteophytes and joint space narrowing.

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The HTLV-1 is the first human retrovirus and is associated with several clinical syndromes, however, the pathogenesis of these clinical manifestations is still not fully understood. Furthermore, there are few complete genomes publicly available, about 0.12 complete genomes per 10,000 infected individuals and the databases have a major deficiency of sequences information. This study generated and characterized 31 HTLV-1 complete genomes sequences derived from individuals with Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (TSP/HAM), Adult T-cell leukemia/lymphoma (ATL), infective dermatitis associated to HTLV-1 (IDH) and asymptomatic patients. These sequences are associated to clinical and epidemiological information about the patients. The sequencing data generated on Ion Torrent PGM platform were assembled and mapped against the reference HTLV-1 genome. These sequences were genotyped as Cosmopolitan subtype, Transcontinental subgroup. We identified the variants in the coding regions of the genome of the different clinical profiles, however, no statistical relation was detected. This study contributed to increase of HTLV-1 complete genomes in the world. Furthermore, to better investigate the contribution of HTLV-1 mutations for the disease outcome it is necessary to evaluate the interaction of the viral genome and characteristics of the human host.

Assuntos

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INTRODUCTION: Bowel dysfunction is frequent in patients with spinal cord diseases, but little is known about the prevalence of bowel symptoms in human T-lymphotropic virus-(HTLV-1) infected individuals. The purpose of this study is to determine the frequency of bowel symptoms in HTLV-1 infected individuals and their correlation with the degree of neurologic disease. METHODS: This is a cross-sectional study comparing the frequency of bowel symptoms in HTLV-1-infected individuals* and seronegative donors (controls). Patients answered a questionnaire, the Rome III Criteria was applied, and stool consistency was evaluated by the Bristol Stool Form Scale. The individuals were classified as HTLV-1 carriers, probable HTLV-1 myelopathy and definitive HTLV-1 associated myelopathy or tropical spastic paraparesis (definitive HAM / TSP)**. RESULTS: We studied 72 HTLV-1 infected individuals and 72 controls with equal age and gender distribution. Constipation was the most frequent complaint, occurring in 38 % of HTLV-1 individuals and in 15 % of the controls. In comparison to the seronegative controls, the probability of constipation occurrence was approximately 18 times higher in definitive HAM / TSP patients. Straining, lumpy or hard stools, sensation of anorectal obstruction/blockage, fewer than 3 defecations per week, flatulence, soiling, evacuation pain, and bleeding were also more frequent in the HTLV-1 patients than in the controls. Moreover, bowel symptoms were more frequent in patients with definitive or probable HAM / TSP than in carriers. CONCLUSIONS: Bowel symptoms were more frequent in HTLV-1-infected patients than in seronegative controls and the frequency of bowel symptoms correlated with the severity of neurologic disease.

Assuntos

Assuntos

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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.

Assuntos

Assuntos

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Abstract INTRODUCTION: Bowel dysfunction is frequent in patients with spinal cord diseases, but little is known about the prevalence of bowel symptoms in human T-lymphotropic virus-(HTLV-1) infected individuals. The purpose of this study is to determine the frequency of bowel symptoms in HTLV-1 infected individuals and their correlation with the degree of neurologic disease. METHODS: This is a cross-sectional study comparing the frequency of bowel symptoms in HTLV-1-infected individuals* and seronegative donors (controls). Patients answered a questionnaire, the Rome III Criteria was applied, and stool consistency was evaluated by the Bristol Stool Form Scale. The individuals were classified as HTLV-1 carriers, probable HTLV-1 myelopathy and definitive HTLV-1 associated myelopathy or tropical spastic paraparesis (definitive HAM / TSP)**. RESULTS: We studied 72 HTLV-1 infected individuals and 72 controls with equal age and gender distribution. Constipation was the most frequent complaint, occurring in 38 % of HTLV-1 individuals and in 15 % of the controls. In comparison to the seronegative controls, the probability of constipation occurrence was approximately 18 times higher in definitive HAM / TSP patients. Straining, lumpy or hard stools, sensation of anorectal obstruction/blockage, fewer than 3 defecations per week, flatulence, soiling, evacuation pain, and bleeding were also more frequent in the HTLV-1 patients than in the controls. Moreover, bowel symptoms were more frequent in patients with definitive or probable HAM / TSP than in carriers. CONCLUSIONS: Bowel symptoms were more frequent in HTLV-1-infected patients than in seronegative controls and the frequency of bowel symptoms correlated with the severity of neurologic disease.

Assuntos

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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.

Assuntos