JORGE SIMAO DO ROSARIO CASSEB
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Dermatologia, Faculdade de Medicina - Docente
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder
12 resultados
Resultados de Busca
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- DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS(2014) ARRUDA, Lia Barbara; ARAUJO, Marilia Ladeira de; MARTINEZ, Maira Luccia; GONSALEZ, Claudio Roberto; DUARTE, Alberto Jose da Silva; COAKLEY, Eoin; LIE, Yolanda; CASSEB, JorgeThe clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno([coreceptor]) analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6% concordance between the phenotypic and genotypic results. Further studies are needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice.
conferenceObject In vitro basal T-cell proliferation and HTLV-1 proviral load among HTLV-1 subjects co-infected with Hepatitis C and/or HIV-1(2015) ASSONE, Tatiane; MITIKO, Tatiana; GOMES, Samara P. C.; PAIVA, Arthur; HAZIOT, Michel; SMID, Jerusa; OLIVEIRA, Augusto Penalva de; NORRIS, Philip J.; CASSEB, Jorge- Relaxation of Adaptive Evolution during the HIV-1 Infection Owing to Reduction of CD4+T Cell Counts(2012) LEAL, Elcio; CASSEB, Jorge; HENDRY, Michael; BUSCH, Michael P.; DIAZ, Ricardo SobhieBackground: The first stages of HIV-1 infection are essential to establish the diversity of virus population within host. It has been suggested that adaptation to host cells and antibody evasion are the leading forces driving HIV evolution at the initial stages of AIDS infection. In order to gain more insights on adaptive HIV-1 evolution, the genetic diversity was evaluated during the infection time in individuals contaminated by the same viral source in an epidemic cluster. Multiple sequences of V3 loop region of the HIV-1 were serially sampled from four individuals: comprising a single blood donor, two blood recipients, and another sexually infected by one of the blood recipients. The diversity of the viral population within each host was analyzed independently in distinct time points during HIV-1 infection. Results: Phylogenetic analysis identified multiple HIV-1 variants transmitted through blood transfusion but the establishing of new infections was initiated by a limited number of viruses. Positive selection (d(N)/d(S)>1) was detected in the viruses within each host in all time points. In the intra-host viruses of the blood donor and of one blood recipient, X4 variants appeared respectively in 1993 and 1989. In both patients X4 variants never reached high frequencies during infection time. The recipient, who X4 variants appeared, developed AIDS but kept narrow and constant immune response against HIV-1 during the infection time. Conclusion: Slowing rates of adaptive evolution and increasing diversity in HIV-1 are consequences of the CD4+ T cells depletion. The dynamic of R5 to X4 shift is not associated with the initial amplitude of humoral immune response or intensity of positive selection.
- Depression is inversely associated with sexual satisfaction and physical function in men living with HIV/AIDS(2016) RASO, Vagner; TOLEA, Magdalena Ioana; CASSEB, Jorge Simão do Rosário; DUARTE, Alberto José da Silva; GREVE, Júlia Maria D'AndréaOBJECTIVE: To assess the associations between depression and physical fitness and function in men living with HIV/AIDS and the role of sexual satisfaction in these associations. DESIGN: Cross-sectional study conducted with 40 males living with HIV/AIDS (40.75 ± 8.68 years [25-66 yrs. old]) divided in two groups based on CD4+ nadir (low nadir < 200 cells/mm3; high nadir ≥ 200 cells/mm3). METHODS: Depression was determined by the Beck Depression Inventory. Participants were asked to evaluate their satisfaction with sexual life and their physical fitness was assessed by flexibility, muscle strength and peak oxygen uptake (VO2peak). Physical function was measured by time taken to move from seated to standing position (TSSP), time to tie sneakers, and time to walk 3.33 m. RESULTS: Depression was inversely associated with sexual satisfaction (for low and high CD4+ nadir) and flexibility (for low CD4+ nadir), and positively associated with walking time (for low CD4+ nadir and total sample), and time to tie sneakers (for the total sample). Sexual satisfaction was positively associated with muscle strength (for low CD4+ nadir and total sample), but inversely with TSSP (for low CD4+ nadir and total sample), walking time (for low CD4+ nadir and total sample), and time to tie sneakers (for high CD4+ nadir and total sample). CONCLUSION: Findings suggest a negative association between depression and physical function regardless of retrospective clinical status of men living with HIV/AIDS and a potential role for sexual satisfaction in explaining this association.
- Low bone mineral density among HIV-infected patients in Brazil(2017) CHABA, Daniela Cardeal da Silva; SOARES, Lismeia R.; PEREIRA, Rosa M. R.; RUTHERFORD, George W.; ASSONE, Tatiane; TAKAYAMA, Liliam; FONSECA, Luiz A. M.; DUARTE, Alberto J. S.; CASSEB, JorgeDecrease in bone mineral density (BMD) has been a complication among people living with HIV/AIDS. To investigate the prevalence of osteopenia/osteoporosis among HIV-infected people living in Sao Paulo city, we studied 108 HIV-infected patients (79 men and 29 women). We extracted data from patients' medical records and BMD was measured by dual-energy X-ray absorptiometry (DXA). Median age of participants was 42 years (interquartile range [IQR] 36-48 years), and the median time since HIV diagnosis was 4.01 years (IQR 2-11 years). Patients had acquired HIV primarily by the sexual route (men who have sex with men 44%, heterosexual 49%). Median age, duration of HIV infection, duration of ART and CD4 nadir were similar for men and women. Plasma viral load was undetectable for 53 patients (49%). Median CD4 T cell count was 399 cells/mu L (IQR 247 - 568). Twenty five patients (23%) had LBMD, and there was no statistically significant difference between men and women (<-1). The associated risk factors for LBMD were older age (>= 50 years old) and smoking with a RR of 3.87 and 2.80, respectively. Thus, despite the lack of statistically significant relationship between the use of ART and LBMD or between duration of ART and LBMD, these factors should be addressed in larger studies.
- Management of HAM/TSP Systematic Review and Consensus-based Recommendations 2019(2021) ARAUJO, Abelardo; BANGHAM, Charles R. M.; CASSEB, Jorge; GOTUZZO, Eduardo; JACOBSON, Steve; MARTIN, Fabiola; OLIVEIRA, Augusto Penalva de; PUCCIONI-SOHLER, Marzia; TAYLOR, Graham P.; YAMANO, YoshihisaPurpose of Review To provide an evidence-based approach to the use of therapies that are prescribed to improve the natural history of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)-a rare disease. Recent Findings All 41 articles on the clinical outcome of disease-modifying therapy for HAM/TSP were included in a systematic review by members of the International Retrovirology Association; we report here the consensus assessment and recommendations. The quality of available evidence is low, based for the most part on observational studies, with only 1 double-masked placebo-controlled randomized trial. Summary There is evidence to support the use of both high-dose pulsed methyl prednisolone for induction and low-dose (5 mg) oral prednisolone as maintenance therapy for progressive disease. There is no evidence to support the use of antiretroviral therapy. There is insufficient evidence to support the use of interferon-alpha as a first-line therapy.
- Polymorphisms in HLA-C and KIR alleles are not associated with HAM/TSP risk in HTLV-1-infected subjects(2018) ASSONE, Tatiane; MALTA, Fernanda M.; BAKKOUR, Sonia; MONTALVO, Leilani; PAIVA, Arthur M.; SMID, Jerusa; OLIVEIRA, Augusto Cesar Penalva de; GONCALVES, Fernanda de Toledo; LUIZ, Olinda do Carmo; FONSECA, Luiz Augusto M.; NORRIS, Philip J.; CASSEB, JorgeIntroduction: Several genetic polymorphisms may be related to susceptibility or resistance to viral disease outcomes. Immunological or genetic factors may act as major triggers of the immune pathogenesis of HAM/TSP. This study investigated the association of immune related genetic polymorphisms with viral and immunological markers. Methods: 247 HTLV-1-infected volunteers, drawn from a larger group of HTLV-infected subjects followed at the Institute of Infectious Diseases ""Emilio Ribas"" (IIER) for up to 19 years, participated in this study, which ran from June 2011 to July 2016. The subjects were classified according to their neurological status into two groups: Group 1 (160 asymptomatic individuals) and Group 2 (87 HAM/TSP patients). Samples were tested for spontaneous lymphocyte proliferation (LPA) and HTLV-1 proviral load (PVL) and for IFN-lambda 4, HLA-C and KIR genotypes using qPCR. Results: We found associations between LPA (p = 0.0001) with HAM/TSP and confirmed the IFN-lambda 4 polymorphism rs8099917, allele GG, as a protective factor using a recessive model (OR = 3.22, CI = 1.10-9.47). Polymorphisms in HLA-C and KIR alleles were not associated with risk of developing HAM/TSP. Conclusion: We demonstrated that age, LPA and an IFN-lambda 4 polymorphism were associated with progression to HAM/TSP. Understanding HAM/TSP pathogenesis can provide important markers of prognostic value for clinical management, and contribute to the discovery of new therapeutic interventions in the future.
- In vitro basal T-cell proliferation among asymptomatic Human T cell Leukemia Virus type 1 patients co-infected with hepatitis C and/or Human Immunodeficiency Virus type 1(2018) ASSONE, Tatiane; KANASHIRO, Tatiana M.; BALDASSIN, Maira P. M.; PAIVA, Arthur; HAZIOT, Michel E.; SMID, Jerusa; OLIVEIRA, Augusto Penalva de; FONSECA, Luiz Augusto M.; NORRIS, Philip J.; CASSEB, JorgeBackground: Infection with Human T cell Leukemia Virus type 1 can be associated with myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory diseases. Lymphocytes from about half of Human T cell Leukemia Virus type 1-infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease and viral burden is poorly understood. Objective: To evaluate T-cell proliferation in vitro among patients co-infected with Human T cell Leukemia Virus type 1/Hepatitis C Virus/Human Immunodeficiency Virus type 1. Material and methods: From 610 Human T cell Leukemia Virus-infected patients of the Human T cell Leukemia Virus outpatient clinic from Institute of Infectious Diseases ""Emilio Ribas"" in Sao Paulo, 273 agreed to participate: 72 had HAM/TSP (excluded from this analysis) and 201 were asymptomatic, a classification performed during a regular neurological appointment. We selected the subgroup made up only by the 201 asymptomatic subjects to avoid bias by the clinical status as a confounder effect, who had laboratory results of Human T cell Leukemia Virus type 1 proviral load and T-cell proliferation assay in our database. They were further grouped according to their serological status in four categories: 121 Human T cell Leukemia Virus type 1 asymptomatic mono-infected carriers; 32 Human T cell Leukemia Virus type 1/Hepatitis C Virus, 29 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1, and 19 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1/Hepatitis C Virus co-infected patients. Clinical data were obtained from medical records and interviews. DNA Human T cell Leukemia Virus type 1 proviral load (PVL) and T-cell proliferation (LPA) assay were performed for all samples. Results: From a total of 273 subjects with Human T cell Leukemia Virus type 1, 80 presented co-infections: 29 had Human Immunodeficiency Virus type 1, 32 had Hepatitis C Virus, and 19 had Human Immunodeficiency Virus type 1 and Hepatitis C Virus. Comparing the groups based on their serological status, independently of being asymptomatic carriers, we observed a significant increase of PVL (p < 0.001) and LPA (p =0.001). However, when groups were stratified according to their clinical and serological status, there was no significant increase in Human T cell Leukemia Virus type 1 PVL and LPA. Conclusion: No significant increase of basal T-cell proliferation among Human T cell Leukemia Virus type 1 co-infected was observed. This interaction may be implicated in liver damage, worsening the prognosis of co-infected patients or, on the contrary, inducing a higher spontaneous clearance of Hepatitis C Virus infection in Human T cell Leukemia Virus type 1 co-infected patients. (C) 2018 Sociedade Brasileira de Infectologia.
- Creation and validation of a bladder dysfunction symptom score for HTLV-1-associated myelopathy/tropical spastic paraparesis(2020) YAMAKAWA, Natsuko; YAGISHITA, Naoko; MATSUO, Tomohiro; YAMAUCHI, Junji; UENO, Takahiko; INOUE, Eisuke; TAKATA, Ayako; NAGASAKA, Misako; ARAYA, Natsumi; HASEGAWA, Daisuke; COLER-REILLY, Ariella; TSUTSUMI, Shuntaro; SATO, Tomoo; ARAUJO, Abelardo; CASSEB, Jorge; GOTUZZO, Eduardo; JACOBSON, Steven; MARTIN, Fabiola; PUCCIONI-SOHLER, Marzia; TAYLOR, Graham P.; YAMANO, YoshihisaBackground Urinary dysfunction is one of the main features of human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, a comprehensive assessment of the severity is difficult because a standardized assessment measure is unavailable. Therefore, this study aimed to develop a novel symptom score for the assessment of urinary dysfunction in HAM/TSP. We interviewed 449 patients with HAM/TSP using four internationally validated questionnaires for assessment of urinary symptoms (27 question items in total): the International Prostate Symptom Score; the International Consultation on Incontinence Questionnaire-Short Form; the Overactive Bladder Symptom Score; and the Nocturia Quality-of-Life questionnaire. We developed a symptom score based on the data of 322 patients who did not use urinary catheters by selecting question items from questionnaires focused on descriptive statistics, correlation analysis, and exploratory factor analysis. The score distribution, reliability, and validity of the developed score were evaluated. Results First, 16 questions related to quality of life, situations, or subjective assessment were omitted from the 27 questions. Exploratory factor analysis revealed that the remaining 11 questions pertained to three factors: frequent urination, urinary incontinence, and voiding symptoms. Three questions, which had similar questions with larger factor loading, were deleted. Finally, we selected eight question items for inclusion in the novel score. The score distribution exhibited no ceiling or floor effect. The Cronbach's alpha (0.737) demonstrated reliable internal consistency. The new score comprised two subscales with acceptable factorial validity (inter-factor correlation coefficient, 0.322): storage symptoms (frequent urination plus urinary incontinence) and voiding symptoms. The correlation between each item and the subscales suggested acceptable construct validity. Conclusions We developed a novel score, the HAM/TSP-Bladder Dysfunction Symptom Score, and demonstrated its reliability and validity. The applicability of this score to patients using catheters should be examined in future research.
- Interferon-gamma Secretion Enzyme-Linked Immunospot Assay Determined Among Human T Cell Lymphotropic Virus Type 1-Infected Subjects: A Potential Laboratory Marker for Early HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Diagnosis(2020) APOLIANO, Carlos Fernando; ASSONE, Tatiane; SILVA, Bosco Christiano Maciel da; CORRAL, Marcelo Andreetta; OLIVEIRA, Augusto Cesar Penalva de; FONSECA, Luiz Augusto Marcondes; DUARTE, Alberto Jose da Silva; TANG, Yuyang; CASSEB, Jorge