LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular
URI Permanente desta comunidade
O Laboratório de Histocompatibilidade e Imunidade Celular é ligado ao Departamento de Cardiopneumologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP).
Linhas de pesquisa: atuação focada no estudo do reconhecimento imunológico através do complexo trimolecular – molécula apresentadora (MHC), peptídeo e molécula de reconhecimento (LTCR) – e das consequências de tal reconhecimento, através de uma resposta de defesa ou de regulação; estuda como modelo as doenças do coração: febre reumática, Chagas ou aterosclerose e também o transplante de órgãos.
Site oficial: http://limhc.fm.usp.br/portal/lim19-laboratorio-de-histocompatibilidade-e-imunidade-celular/
Linhas de pesquisa: atuação focada no estudo do reconhecimento imunológico através do complexo trimolecular – molécula apresentadora (MHC), peptídeo e molécula de reconhecimento (LTCR) – e das consequências de tal reconhecimento, através de uma resposta de defesa ou de regulação; estuda como modelo as doenças do coração: febre reumática, Chagas ou aterosclerose e também o transplante de órgãos.
Site oficial: http://limhc.fm.usp.br/portal/lim19-laboratorio-de-histocompatibilidade-e-imunidade-celular/
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- LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular
- LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular
- LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular
Submissões Recentes
Thinking out of the box: revisiting health surveillance based on medical records
(2023) SAMPAIO, V. S.; LOPES, R.; OZAHATA, M. C.; NAKAYA, H. I.; SOUSA, E.; ARAúJO, J. D.; BRAGATTE, M. A. S.; BRITO, A. F.; GRESPAN, R. M. Z.; CAPUANI, M. L. D.; DOMINGUES, H. H.; PELLINI, A. C. G.; MATEOS, S. D. O. G.; CONDE, M. T. R. P.; LEAL, F. Eudes; SABINO, E.; SIMãO, M.; KALIL, J.
Despite the considerable advances in the last years, the health information systems for health surveillance still need to overcome some critical issues so that epidemic detection can be performed in real time. For instance, despite the efforts of the Brazilian Ministry of Health (MoH) to make COVID-19 data available during the pandemic, delays due to data entry and data availability posed an additional threat to disease monitoring. Here, we propose a complementary approach by using electronic medical records (EMRs) data collected in real time to generate a system to enable insights from the local health surveillance system personnel. As a proof of concept, we assessed data from São Caetano do Sul City (SCS), São Paulo, Brazil. We used the fever term as a sentinel event. Regular expression techniques were applied to detect febrile diseases. Other specific terms such as malaria, dengue, Zika, or any infectious disease were included in the dictionary and mapped to fever. Additionally, after tokenizing, we assessed the frequencies of most mentioned terms when fever was also mentioned in the patient complaint. The findings allowed us to detect the overlapping outbreaks of both COVID-19 Omicron BA.1 subvariant and Influenza A virus, which were confirmed by our team by analyzing data from private laboratories and another COVID-19 public monitoring system. Timely information generated from EMRs will be a very important tool to the decision-making process as well as research in epidemiology. Quality and security on the data produced is of paramount importance to allow the use by health surveillance systems.
ABX464 (obefazimod) for patients with COVID-19 at risk for severe disease: miR-AGE, a randomized, double-blind placebo-controlled trial
(2023) GIAVINA-BIANCHI, P.; CUA, E.; RISSO, K.; MONDAIN, V.; VISSIAN, A.; JOIE, C.; POULETTY, P.; GINESTE, P.; EHRLICH, H. J.; KALIL, J.
Background: ABX464 (obefazimod) is a small molecule that upregulates a single microRNA (miR-124) in immune cells and reduces the production of various inflammatory cytokines and chemokines. Objective: We assessed the efficacy and safety of the standard of care (SoC) plus oral obefazimod (SoC plus ABX464), 50 mg once daily, versus the SoC plus placebo for prevention of severe acute respiratory syndrome in patients with coronavirus disease 2019 (COVID-19) who are at risk for severe disease. Methods: Eligible patients for this phase 2/3 double-blind, placebo-controlled miR-AGE study were randomized (2:1) into 2 groups: SoC-ABX464 (n = 339) and SoC-placebo (n = 170). The primary end point was the percentage of patients who did not require use of high-flow oxygen or invasive or noninvasive mechanical ventilation within 28 days. The safety analyses included patients who had been randomly assigned and had received at least 1 dose of the study treatment. Results: At the time of the interim analysis, obefazimod showed no benefit over placebo when added to the SoC; the study enrollment was stopped for futility. The evaluation of the safety of obefazimod in 505 patients showed significantly more treatment-emergent adverse events in the SoC-ABX464 group than in the SoC-placebo group (P = .007). Frequently reported AEs in the SoC-ABX464 group included headache (14.6%), abdominal pain (9.6%), diarrhea (9.0%), back pain (6.9%), and nausea (6.0%). No treatment-related changes in laboratory parameters were reported. Conclusion: For patients who have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and are at risk for severe COVID-19, obefazimod, 50 mg, provided no benefit over placebo when added to the SoC, although it did have a good safety profile (comparable to that reported in many therapeutic areas).
Occupational asthma and allergic asthma: differences in the physical activity level, clinical control, and airway inflammation
(2023) SILVA, Ronaldo Aparecido Da; FREITAS, Lucas Rodrigues Silva; ALMEIDA, Francine Maria De; GALVAO, Clovis Eduardo Santos; NOGUEIRA, Soraia Felix; BEZERRA, Suellen Karoline Moreira; CARVALHO, Celso Ricardo Fernades De; ARAUJO, Kaique Alves De; CRUZ, Fabiola Matos Da; AGONDI, Rosana Camara; MARTINS, Milton Arruda; TIBERIO, Iolanda De Fatima Lopes Calvo; SARAIVA-ROMANHOLO, Beatriz Mangueira
Characteristics and benefits of responders to a behavioral intervention to increase physical activity in asthma: preliminary data from a pragmatic study
(2023) LIMA, Fabiano de; LUNARDI, Adriana; PINHEIRO, David; SOUZA, Joao Victor De; STELMACH, Rafael; AGONDI, Rosana; GIAVINA-BIANCHI, Pedro; CARVALHO-PINTO, Regina; CARVALHO, Celso
Effect of adjuvant probiotic therapy (Lactobacillus reuteri) in the treatment of periodontitis associated with diabetes mellitus: clinical, controlled, and randomized study
(2024) JARDINI, Maria Aparecida Neves; PEDROSO, Juliana Fatima; FERREIRA, Camila Lopes; NUNES, Camilla Magnoni Moretto; REICHERT, Cadiele Oliana; ALDIN, Marlene Nunez; FIGUEIREDO NETO, Antonio Martins; LEVY, Debora; DAMASCENO, Nagila Raquel Teixeira
Objectives Subgingival instrumentation (SI) with probiotics may be a proposal for the treatment of periodontitis (P), for patients with type 2 diabetes mellitus (T2DM). The Lactobacillus reuteri probiotic as an adjunctive therapy in the treatment of P associated with T2DM was evaluated.Materials and methods Forty diabetic participants diagnosed with P (stage III and IV, grade B) were randomized into SI + Placebo (n = 20): subgingival instrumentation plus placebo lozenges and SI + Probi (n = 20): subgingival instrumentation plus probiotics. Probing depth (PD), gingival recession (GR), clinical attachment level (CAL), plaque index (PI), bleeding on probing (BoP), and PISA index were performed at baseline and 30, 90, and 180 days. Cytokine concentration in the gingival crevicular fluid, subgingival biofilm sample, and LDL and HDL subfractions were evaluated.Results In the deep pockets, PD in SI + Probi showed increased values (p = 0.02) compared to SI + Placebo at 90 days. For CAL, SI + Probi showed increased values compared to SI + Placebo, with a significant difference at 30 days (p = 0.03), 90 days (p = 0.02), and 180 days (p = 0.04). At #PD >= 7 mm, SI + Probi had a more frequent number of sites (p = 0.03) compared to SI + Placebo only at baseline. For the PISA, SI + Probi showed a significant difference (p = 0.04) compared to SI + Placebo at 90 days. For cytokines, SI + Probi showed higher quantification than SI + Placebo for IL-10 (p < 0.001) at 90 days, IL-12 (p = 0.010) at 90 days, IL-1 beta (p = 0.035) at 90 days, and IL-8 (p = 0.003) at baseline. SI + Placebo showed higher quantification of IL-1 beta (p = 0.041) compared to SI + Probi only at 30 days. There was a reduction in all microbial complexes. SI + Probi improved LDL size (246.7 nm vs 260.4 nm; p < 0.001), while large HDL subfractions were reduced aft 180 days of treatment (24.0% vs 20.3%; p = 0.022) when compared with SI + Placebo; this response was dependent of probiotics (1.0 mg/dL vs - 6.2 mg/dL; p = 0.002).Conclusion Subgingival instrumentation improved the clinical periodontal parameters in patients with T2DM. The use of L. reuteri probiotics had no additional effects compared with the placebo; however, there was a positive effect on the lipoprotein subfraction.
Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil
(2024) SUNDERRAJ, Ashwin; CUNHA, Luisa Marin; AVILA, Matheus; ALEXANDRIA, Shaina; FERREIRA, Ariela Mota; SILVA, Lea Campos de Oliveira-da; RIBEIRO, Antonio L. P.; NUNES, Maria do Carmo Pereira; SABINO, Ester C.; LANDAY, Alan; KALIL, Jorge; CHEVILLARD, Christophe; CUNHA-NETO, Edecio; FEINSTEIN, Matthew J.
Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and Sao Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.
Vaccines past and future - a Brazilian perspective
(2023) KALIL, Jorge
In this opinion article, I provide a brief history of vaccine development, commenting on the classic ways of obtaining vaccines using the infectious agent itself. Then, I address the issue of viral vaccines, their successes , difficulties, discussing the issue of viral serotypes. Bacterial vaccines and their relative success. I present our studies on Rheumatic Heart Disease and the development of an anti-streptococcal vaccine. Then, I discuss vaccine development platforms, especially with the successes achieved with non-replicating viral vector vaccines and, above all, the great success of mRNA vaccines. mRNA vaccines were only possible after the advances obtained with the replacement of nucleotides that reduced the action of innate immunity. Will all vaccines be made from mRNA in the future? Next, I address the issue of vaccine administration routes, whether subcutaneously, intradermally, intramuscularly or nasal instillation. I expose data from my laboratory on the development of an intranasal vaccine that induced a protective mucosal response, preventing infection , consequently the transmission of the SARS-CoV-2 virus. Then, I discuss which future vaccines could be developed beyond acute infectious diseases. Finally, I discuss the advantages of developing safe, effective, multiple-use vaccines and how to make them accessible to the world's population by promoting health equity.
Fructose biphosphate aldolase: A new cassava allergen
(2023) VENTURA, Anne K. R. M.; ALVES, Safiri de P.; CASTRO, Roberta A.; ROSSINI, Bruno C.; DELAZARI, Lucilense S.; OLIVEIRA, Amanda M. de; MORETTI, Ana I. S.; CASTRO, Fabio F. M.; KALIL, Jorge; YANG, Ariana C.; SANTOS, Keity S.
Background: Food allergy has considerably increased in recent years and this situation has been aggravated mainly by the consumption of more processed and complex foods, since minor or potentially allergenic foods are not required to be labeled. Manihot esculenta (cassava) is a widely consumed food in South America, Africa, and Asia and can be used in the production of flour and starch, as well as several other products. This root can cause allergic reactions with symptoms ranging from mild to severe. Methods: Thus, the aim of this study was the characterization of the immunogenic cassava proteins responsible for sensitizing patients allergic to it. Using a 2D-SDS-PAGE based proteomic approach, six proteins were identified, including Fructose Bisphosphate Aldolase (FBA). Recom-binant FBA was produced in Expi293 cells and evaluated by immunoblotting with the serum of 10 individual study subjects. Results: Our results showed six cassava IgE-reactive proteins. From those, recombinant fructose bisphosphate aldolase (FBA) showed a positivity of 80% among tested sera, proving to be a highly sensitizing protein. Conclusion: The recombinant FBA molecule obtained in this study can be important for in vivo diagnostic assays, by producing more accurate results, and for desensitization protocols, in which the use of the isolated molecule produces more precise results by avoiding secondary sensitization. Trial registration: All patients signed a consent form approved by the internal ethics committee CAPPesq, Comissao de etica para Analise de Projetos de Pesquisa do HC FMUSP (CAAE: 10420619.6.0000.0068).
Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase
(2021) SAHLY, H. M. El; BADEN, L. R.; ESSINK, B.; DOBLECKI-LEWIS, S.; MARTIN, J. M.; ANDERSON, E. J.; CAMPBELL, T. B.; CLARK, J.; JACKSON, L. A.; FICHTENBAUM, C. J.; ZERVOS, M.; RANKIN, B.; EDER, F.; FELDMAN, G.; KENNELLY, C.; HAN-CONRAD, L.; LEVIN, M.; NEUZIL, K. M.; COREY, L.; GILBERT, P.; JANES, H.; FOLLMANN, D.; MAROVICH, M.; POLAKOWSKI, L.; MASCOLA, J. R.; LEDGERWOOD, J. E.; GRAHAM, B. S.; AUGUST, A.; CLOUTING, H.; DENG, W.; HAN, S.; LEAV, B.; MANZO, D.; PAJON, R.; SCHODEL, F.; TOMASSINI, J. E.; ZHOU, H.; MILLER, J.
BACKGROUND At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported. METHODS We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 mu g) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021. RESULTS The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mitNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified. CONCLUSIONS The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed.
COVID-19 mechanisms on cardio-vascular dysfunction: from membrane receptors to immune response, volume II
(2023) MORETTI, Ana Iochabel Soares; SCHREIBER, Roberto; WANSCHEL, Amarylis B. A.