Radiographic aspects in individuals infected by human T-lymphotropic virus type 1 (HTLV-1) with joint pain.

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.

Radiographic aspects in individuals infected by human T-lymphotropic virus type 1 (HTLV-1) with joint pain

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.

Complete genome sequence of human T-cell lymphotropic type 1 from patients with different clinical profiles, including infective dermatitis.

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.

Prevalence of Bowel Symptoms in Patients Infected with Human T-Lymphotropic type 1 Virus.

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.

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

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.

Prevalence of bowel symptoms in patients infected with human T-lymphotropic type 1 virus

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.

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.

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.

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.

In Vitro Immunomodulatory Activity of a Transition-State Analog Inhibitor of Human Purine Nucleoside Phosphorylase in Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL) is the most common clinical form of American tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis. CL is associated with a strong Th1 immune response. This exacerbated inflammatory response is correlated with severity of disease and delays the healing time of the ulcer. The fourth-generation immucillin derivative (DI4G), a potent inhibitor of purine nucleoside phosphorylase, has been proposed as a promising agent in the treatment of diseases associated with T cell activation. Herein, we evaluated the in vitro immunomodulatory activity of DI4G in cells of patients presenting with CL. Peripheral blood mononuclear cells (PBMC) from CL patients were stimulated with soluble leishmania antigen (SLA), in the presence or absence of DI4G, and IFN-γ, TNF, CXCL9, and CXCL10 levels were determined by ELISA. Lymphocyte proliferation in the presence or absence of DI4G was also evaluated, using flow cytometry. DI4G was able to decrease (p < 0.05) IFN-γ production but did not change the TNF, CXCL9, and CXCL10 levels. DI4G decreased (p < 0.05) the lymphoproliferative response mediated by CD8+ T cells, but not that by CD4+ T cells. DI4G is able to attenuate the exaggerated immune response in CL, exhibiting immunomodulatory activity in IFN-γ production and in CD8+ T cell proliferation.

Oral Pentoxifylline Associated with Pentavalent Antimony: A Randomized Trial for Cutaneous Leishmaniasis.

AbstractCutaneous leishmaniasis (CL) by Leishmania braziliensis is associated with decreasing cure rates in Brazil. Standard treatment with pentavalent antimony (Sbv) cures only 50-60% of the cases. The immunopathogenesis of CL ulcer is associated with high interferon-γ and tumor necrosis factor (TNF) production. Pentoxifylline, a TNF inhibitor, has been successfully used in association with Sbv in mucosal and cutaneous leishmaniasis. This randomized, double-blind, and placebo-controlled trial aimed to evaluate the efficacy and safety of oral pentoxifylline plus Sbv versus placebo plus Sbv in patients with CL in Bahia, Brazil. A total of 164 patients were randomized in two groups to receive the combination or the monotherapy. Cure rate 6 months after treatment was 45% in the pentoxifylline group and 43% in the control group. There was also no difference between the groups regarding the healing time (99.7 ± 66.2 days and 98.1 ± 72.7 days, respectively). Adverse events were more common in the pentoxifylline group (37.8%), versus 23% in the placebo group. This trial shows that Sbv combined therapy with pentoxifylline is not more effective than Sbv monotherapy in the treatment of CL caused by L. braziliensis.

Inflammatory and immunological profiles in patients with COPD: relationship with FEV 1 reversibility.

OBJECTIVE:: To determine whether COPD severity correlates with sputum cell counts, atopy, and asthma. METHODS:: This was a cross-sectional study involving 37 patients with COPD and 22 healthy subjects with normal lung function (controls). Sputum cell counts were determined by microscopy after centrifugation of samples. Skin prick tests were performed, and serum cytokines were determined by ELISA. RESULTS:: Patients were stratified by bronchodilator response: a non-reversible airflow limitation (nonRAL) group comprised 24 patients showing no significant post-bronchodilator change in FEV1; and a partially reversible airflow limitation (partialRAL) group comprised 13 patients showing FEV1 reversibility (post-bronchodilator FEV1 increase ≥ 12%). The proportion of eosinophils in sputum was higher in the partialRAL group than in the nonRAL group (p < 0.01), and there was an inverse correlation between the proportion of eosinophils and FEV1 (p < 0.05). However, none of the patients had a history of asthma and skin prick test results did not differ between the two groups. In the patient sputum samples, neutrophils predominated. Serum levels of TNF, IL-6, IL-8, and RANTES (CCL5) were higher in patients than in controls (p < 0.001) but did not differ between the two patient groups. CONCLUSIONS:: COPD patients with partial FEV1 reversibility appear to have higher sputum eosinophil counts and greater airway hyperresponsiveness than do those with no FEV1 reversibility. However, we found that COPD severity did not correlate with atopy or with the cytokine profile. OBJETIVO:: Determinar se a gravidade da DPOC se correlaciona com a contagem de células no escarro, atopia e asma. MÉTODOS:: Estudo transversal com 37 pacientes com DPOC e 22 indivíduos saudáveis com função pulmonar normal (controles). As contagens de células no escarro foram determinadas por microscopia após a centrifugação das amostras. Foram realizados testes cutâneos de puntura, e as citocinas séricas foram determinadas por ELISA. RESULTADOS:: Os pacientes foram estratificados pela resposta ao broncodilatador: o grupo de limitação ao fluxo aéreo não reversível (LFAnr) envolveu 24 pacientes sem alteração significativa do VEF1 pós-broncodilatador, e o grupo de limitação ao fluxo aéreo parcialmente reversível (LFApr) envolveu 13 pacientes com reversibilidade do VEF1 (aumento do VEF1 pós-broncodilatador ≥ 12%). A proporção de eosinófilos no escarro foi maior no grupo LFApr do que no LFAnr (p < 0,01), e houve uma correlação inversa entre a proporção de eosinófilos e VEF1 (p < 0,05). Entretanto, nenhum dos pacientes apresentou histórico de asma e os resultados dos testes cutâneos não diferiram entre os dois grupos. Nas amostras de escarro dos pacientes, os neutrófilos predominaram. Os níveis séricos de TNF, IL-6, IL-8 e RANTES (CCL5) foram maiores nos pacientes que nos controles (p < 0,001), mas não diferiram entre os dois grupos de pacientes. CONCLUSÕES:: Pacientes com DPOC e reversibilidade parcial do VEF1 parecem apresentar maiores contagens de eosinófilos no escarro e maior hiper-responsividade das vias aéreas que aqueles sem reversibilidade do VEF1. Entretanto, a gravidade da DPOC não se correlacionou com atopia ou perfil das citocinas.