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
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- IL28B Gene Polymorphism SNP rs8099917 Genotype GG Is Associated with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in HTLV-1 Carriers(2014) ASSONE, Tatiane; SOUZA, Fernando Vieira de; GAESTER, Karen Oliveira; FONSECA, Luiz Augusto Marcondes; LUIZ, Olinda do Carmo; MALTA, Fernanda; PINHO, Joao Renato Rebello; GONCALVES, Fernanda de Toledo; DUARTE, Alberto Jose da Silva; OLIVEIRA, Augusto Cesar Penalva de; CASSEB, JorgeBackground: The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. Methods: The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. Results: A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95% = 1.82-31.72). Conclusion: Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.
- Living Invisible: HTLV-1-Infected Persons and the Lack of Care in Public Health(2012) ZIHLMANN, Karina Franco; ALVARENGA, Augusta Thereza de; CASSEB, JorgeIntroduction: Human T-cell lymphotropic virus type 1 (HTLV-1) infection is intractable and endemic in many countries. Although a few individuals have severe symptoms, most patients remain asymptomatic throughout their lives and their infections may be unknown to many health professionals. HTLV-1 can be considered a neglected public health problem and there are not many studies specifically on patients' needs and emotional experiences. Objective: To better understand how women and men living with HTLV-1 experience the disease and what issues exist in their healthcare processes. Methods: A qualitative study using participant observation and life story interview methods was conducted with 13 symptomatic and asymptomatic patients, at the outpatient clinic of the Emilio Ribas Infectious Diseases Institute, in Sao Paulo, Brazil. Results and Discussion: The interviewees stated that HTLV-1 is a largely unknown infection to society and health professionals. Counseling is rare, but when it occurs, focuses on the low probability of developing HTLV-1 related diseases without adequately addressing the risk of infection transmission or reproductive decisions. The diagnosis of HTLV-1 can remain a stigmatized secret as patients deny their situations. As a consequence, the disease remains invisible and there are potentially negative implications for patient self-care and the identification of infected relatives. This perception seems to be shared by some health professionals who do not appear to understand the importance of preventing new infections. Conclusions: Patients and medical staff referred that the main focus was the illness risk, but not the identification of infected relatives to prevent new infections. This biomedical model of care makes prevention difficult, contributes to the lack of care in public health for HTLV-1, and further perpetuates the infection among populations. Thus, HTLV-1 patients experience an ""invisibility"" of their complex demands and feel that their rights as citizens are ignored.
- Human T-cell leukemia virus type 1 infection among Japanese immigrants and their descendants living in Southeast Brazil: A call for preventive and control responses(2021) BANDEIRA, Larissa M.; PUGA, Marco A. M.; WEIS-TORRES, Sabrina M. S.; REZENDE, Grazielli R.; DOMINGOS, Joao A.; TANAKA, Tayana S. O.; CESAR, Gabriela A.; NUKUI, Youko; VICENTE, Ana C. P.; CASSEB, Jorge; YAMASHIRO, Juliana; SEGURADO, Aluisio C.; SAITO, Murilo O.; PINHO, Joao R. R.; V, Rivaldo Cunha; OKUMOTO, Osnei; UEHARA, Silvia N. O.; MOTTA-CASTRO, Ana R. C.Human T-cell leukemia virus type 1 (HTLV-1) has worldwide distribution and is considered endemic in southwestern Japan. HTLV-1 infection has been associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) besides other diseases. This cross-sectional study aimed to investigate the prevalence, risk factors and molecular characterization of HTLV-1, among the world's largest population of Japanese immigrants and their descendants outside of Japan, in Sao Paulo, Southeast Brazil, as well as to analyze the phylogenetic relationship among isolates of HTLV-1. From July to December 2017, 2,139 individuals from five Japanese associations were interviewed and submitted to blood collection. All serum samples were first tested for the presence of anti-HTLV-1/2 antibodies by ELISA and then peripheral blood from individuals with positive serological results were analyzed for the presence of HTLV-1 5'LTR proviral DNA. Partial sequencing of the 5'LTR region of HTLV-1 proviral DNA was performed by Sanger. The prevalence of HTLV-1 infection was 5.1% (CI 95%: 4.2-6.0). In the multiple logistic regression model, HTLV-1 infection was associated with age >= 45 years, female sex, being first and second-generation Japanese immigrants, and having sexual partners with history of blood transfusion. The phylogenetic analysis revealed that all HTLV-1 were classified as Cosmopolitan (1a) subtype. Of them, 47.8% were classified as Transcontinental (A) subgroup and 52.2% as belonging to the Japanese (B) subgroup. Although most HTLV-1-infected patients were asymptomatic (97.3%), blurred vision was associated with HTLV-1 infection. The high prevalence of HTLV-1 infection found in this studied population and especially the intra- and interfamily HTLV-1 transmission presents an urgent call for preventive and control responses of this infection in Brazil. Author summary What is the prevalence of HTLV-1 among the largest world population of Japanese immigrants and their descendants outside Japan? There are approximately 1.5 million people of Japanese descent in Brazil and most of them living in Sao Paulo state, Southeast Brazil. The prevalence of HTLV-1 infection was 5.1% among 2,139 individuals from five Japanese associations in Sao Paulo. The prevalence of 5.1% (95% CI: 4.2-6.0) of HTLV-1 infection found in this study is higher than those observed in other studies conducted in HTLV-1 endemic areas and in specific groups at high risk from Brazil. Among HTLV-infected individuals, the majority (86.2%) were unaware of their HTLV diagnosis. The HTLV-1 infection was associated with the age >= 45 years, being the first and second generation of Japanese immigrants, and having sexual partners with a history of blood transfusion. Epidemiological data, along with molecular results also demonstrated high occurrence of similar sequences transmitted intra- and interfamily. The high prevalence of HTLV-1 infection found in this studied population presents an urgent call for preventive and control responses of this infection in Brazil.
- Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load(2019) HAZIOT, Michel E.; GASCON, M. Rita; ASSONE, Tatiane; FONSECA, Luiz Augusto M.; LUIZ, Olinda do Carmo; SMID, Jerusa; PAIVA, Arthur M.; MARCUSSO, Rosa Maria do N.; OLIVEIRA, A. C. Penalva de; CASSEB, JorgeSeveral studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). Methods: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases Emilio Ribas, SAo Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). Results: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. Conclusions: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as ""asymptomatic"", who we reclassified as having an intermediate syndrome. Author summary At least 5-10 million people live with the Human T-Cell Lymphotropic Virus type 1 (HTLV-1) worldwide, and around 0.25-5% of them may develop HTLV-1-associated myelopathy/Tropical spastic paraparesis (HAM/TSP), which is associated with chronic inflammation. In this study, involving 175 HTLV-1-infected subjects originally classified as asymptomatic, we found that 42 of them in reality presented some early clinical conditions, including alterations related not only to the neurological system, but also to the eyes and the skin. We called such conditions intermediate syndrome. Thus, it seems reasonable to suggest that all HTLV-1-infected subjects should be monitored for symptoms that may arise earlier in the course of their infection.
- Health state utility values in people living with HTLV-1 and in patients with HAM/TSP: The impact of a neglected disease on the quality of life(2020) ROSADAS, Carolina; ASSONE, Tatiane; YAMASHITA, Marina; ADONIS, Adine; PUCCIONI-SOHLER, Marzia; SANTOS, Marisa; PAIVA, Arthur; CASSEB, Jorge; OLIVEIRA, Augusto C. P.; TAYLOR, Graham P.Author summary HTLV-1 is a life-long persistent infection with no curative treatment available. It can cause a disabling neurological disease (HAM/TSP). Public policies aiming HTLV-1 prevention are important. Cost-utility studies are essential to identify which policies should be implemented. These studies have been hampered by the lack of information about health state utility values in patients with HAM/TSP and asymptomatic carriers (AC). These values represent the quality of life (QoL) and may vary from 0 (death) to 1 (best health state). We determined these values for AC (0.7121) and HAM/TSP patients (0.2991) using a self-administered questionnaire in patients from Brazil and UK. QoL in patients with HAM/TSP is lower than that reported for more than 130 other conditions with such data, including multiple sclerosis, neuropathic pain, Parkinson's disease and HIV infection. For 12% of patients with HAM/TSP QoL was worse than death. Disease severity, rather than duration of disease, is associated with decreased QoL in HAM/TSP. HTLV-1 AC have impaired QoL compared to the general population in both countries. The data presented here will inform proper economic analysis in order to identify cost-effective policies. This is especially important for low- and middle-income countries where HTLV-1 prevalence is high and resources are limited. Background: HTLV-1 is a neglected sexually transmitted infection despite being the cause of disabling neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is no treatment for this infection and public health policies are essential to reduce its transmission. However, there are no data to support adequate cost-effective analysis in this field. The aim of this study was to obtain health state utility values for individuals with HAM/TSP and HTLV-1 asymptomatic carriers (AC). The impact of both states on quality of life (QoL) is described and compared to other diseases. Methods: A cross-sectional observational study of 141 individuals infected with HTLV-1 (79 with HAM/TSP and 62 AC) from three Brazilian states (Rio de Janeiro, Sao Paulo and Alagoas) and from the United Kingdom. Participants completed a validated general health questionnaire (EQ-5D, Euroqol) from which country specific health state utility values are generated. Clinical and epidemiological data were collated. Principal findings: Health state utility value for HAM/TSP was 0.2991. QoL for 130 reported clinical conditions ranges from 0.35 to 0.847. 12% reported their quality of life as worse as death. Low QoL was associated with severity rather than duration of disease with a moderate inverse correlation between QoL and Osame's Motor Disability Score (-0.4933) Patients who are wheelchair dependent had lowest QoL whilst those still walking unaided had the highest. AC also reported impaired QoL (0.7121) compared to general population. Conclusion: HTLV-1 and its associated neurological disease has a marked impact on QoL. This study provides robust data to support the development of cost-utility analysis of interventions for HTLV-1.
- Immunoprofiling of fresh HAM/TSP blood samples show altered innate cell responsiveness(2021) ROCAMONDE, Brenda; FUTSCH, Nicolas; ORII, Noemia; ALLATIF, Omran; OLIVEIRA, Augusto Cesar Penalva de; MAHIEUX, Renaud; CASSEB, Jorge; DUTARTRE, HeleneAuthor summary The infection by the Human T-cell Leukemia Virus-1 (HTLV-1) is quite frequent in Brazil. Between 1-5% of infected individuals develop a devastating neurodegenerative disease (HAM/TSP) as a result of a sustained inflammation in the central nervous system, with no effective treatment. So far, inflammation has been linked to the deregulated activation of T-cells, but the role of innate cells has not been investigated yet. In this work, we aimed to characterize the responsiveness of innate cells, as this immune population is cornerstone of efficient immune response, but also might participate in disease exacerbation found in chronic infection. Our findings suggest an impaired antiviral response and increased inflammatory responsiveness by dendritic cells and monocytes in HAM/TSP patients compared to asymptomatic carriers. This sustained inflammatory responsiveness upon innate cell activation could participate in the establishment of the HAM/TSP disease. The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. Immune cell from the adaptive compartment are involved in disease manifestation but whether innate cell functions participate in disease occurrence has not been evaluated. In this study, we analyzed innate cell responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower response of IFN alpha(+) DCs and monocytes in HAM/TSP compared to asymptomatic carriers, as a potential consequence of corticosteroid treatments. In contrast, a higher frequency of monocytes producing MIP-1 alpha and pDC producing IL-12 was detected in HAM/TSP blood samples, together with higher IFN gamma responsiveness of NK cells, suggesting an increase sensitivity to inflammatory response in HAM/TSP patients compared to asymptomatic carriers. This sustained inflammatory responsiveness could be linked or be at the origin of the neuroinflammatory status in HAM/TSP patients. Therefore, the mechanism underlying this dysregulations could shed light onto the origins of HAM/TSP disease.
- High Prevalence of Skin Disorders among HTLV-1 Infected Individuals Independent of Clinical Status(2013) OKAJIMA, Renata; OLIVEIRA, Augusto C. P.; SMID, Jerusa; CASSEB, Jorge; SANCHES JR., Jose AntonioBackground: Human T-cell lymphotropic virus type 1 (HTLV-1) infection can increase the risk of developing skin disorders. This study evaluated the correlation between HTLV-1 proviral load and CD4(+) and CD8(+) T cells count among HTLV-1 infected individuals, with or without skin disorders (SD) associated with HTLV-1 infection [SD-HTLV-1: xerosis/ichthyosis, seborrheic dermatitis or infective dermatitis associated to HTLV-1 (IDH)]. Methods: A total of 193 HTLV-1-infected subjects underwent an interview, dermatological examination, initial HTLV-1 proviral load assay, CD4(+) and CD8(+) T cells count, and lymphproliferation assay (LPA). Results: A total of 147 patients had an abnormal skin condition; 116 (79%) of them also had SD-HTLV-1 and 21% had other dermatological diagnoses. The most prevalent SD-HTLV-1 was xerosis/acquired ichthyosis (48%), followed by seborrheic dermatitis (28%). Patients with SD-HTLV-1 were older (51 vs. 47 years), had a higher prevalence of myelopathy/tropical spastic paraparesis (HAM/TSP) (75%), and had an increased first HTLV-1 proviral load and basal LPA compared with patients without SD-HTLV-1. When excluding HAM/TSP patients, the first HTLV-1 proviral load of SD-HTLV-1 individuals remains higher than no SD-HTLV-1 patients. Conclusions: There was a high prevalence of skin disorders (76%) among HTLV-1-infected individuals, regardless of clinical status, and 60% of these diseases are considered skin disease associated with HTLV-1 infection.