LIM/60 - Laboratório de Imunologia Clínica e Alergia
URI Permanente desta comunidade
O Laboratório de Imunologia Clínica e Alergia é ligado ao Departamento de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo (FMUSP).
Linhas de pesquisa: doenças alérgicas respiratórias e cutâneas; bioinformática; autoimunidade; imunologia de tumores; imunodeficiência secundária ao HIV; imunodeficiências primárias e imunologia em doenças infecciosas.
Site oficial: http://limhc.fm.usp.br/portal/lim60-laboratorio-de-imunologia-clinica-e-alergia/
Linhas de pesquisa: doenças alérgicas respiratórias e cutâneas; bioinformática; autoimunidade; imunologia de tumores; imunodeficiência secundária ao HIV; imunodeficiências primárias e imunologia em doenças infecciosas.
Site oficial: http://limhc.fm.usp.br/portal/lim60-laboratorio-de-imunologia-clinica-e-alergia/
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- LIM/60 - Laboratório de Imunologia Clínica e Alergia
- LIM/60 - Laboratório de Imunologia Clínica e Alergia
- LIM/60 - Laboratório de Imunologia Clínica e Alergia
Submissões Recentes
Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic
(2024) RITTO, Ana Paula; ARAUJO, Adriana Ladeira de; CARVALHO, Carlos Roberto Ribeiro de; SOUZA, Heraldo Possolo De; FAVARETTO, Patricia Manga e Silva; SABOYA, Vivian Renata Boldrim; GARCIA, Michelle Louvaes; KULIKOWSKI, Leslie Domenici; KALLAS, Esper Georges; PEREIRA, Antonio Jose Rodrigues; COBELLO JUNIOR, Vilson; SILVA, Katia Regina; ABDALLA, Eidi Raquel Franco; SEGURADO, Aluisio Augusto Cotrim; SABINO, Ester Cerdeira; RIBEIRO JUNIOR, Ulysses; FRANCISCO, Rossana Pulcineli Vieira; MIETHKE-MORAIS, Anna; LEVIN, Anna Sara Shafferman; SAWAMURA, Marcio Valente Yamada; FERREIRA, Juliana Carvalho; SILVA, Clovis Artur; MAUAD, Thais; GOUVEIA, Nelson da Cruz; LETAIF, Leila Suemi Harima; BEGO, Marco Antonio; BATTISTELLA, Linamara Rizzo; DUARTE, Alberto Jose da Silva; SEELAENDER, Marilia Cerqueira Leite; MARCHINI, Julio; FORLENZA, Orestes Vicente; ROCHA, Vanderson Geraldo; MENDES-CORREA, Maria Cassia; COSTA, Silvia Figueiredo; CERRI, Giovanni Guido; BONFA, Eloisa Silva Dutra de Oliveira; CHAMMAS, Roger; BARROS FILHO, Tarcisio Eloy Pessoa de; BUSATTO FILHO, Geraldo
Introduction The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.Methods At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.Results Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.Discussion Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.
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).
Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing
(2023) CLARO, I. M.; RAMUNDO, M. S.; COLETTI, T. M.; SILVA, C. A. M. da; VALENCA, I. N.; CANDIDO, D. S.; SALES, F. C. S.; MANULI, E. R.; JESUS, J. G. de; PAULA, A. de; FELIX, A. C.; ANDRADE, P. D. S.; PINHO, M. C.; SOUZA, W. M.; AMORIM, M. R.; PROENCA-MODENA, J. L.; KALLAS, E. G.; LEVI, J. E.; FARIA, N. R.; SABINO, E. C.; LOMAN, N. J.; QUICK, J.
Emerging and re-emerging viruses are a global health concern. Genome sequencing as an approach for monitoring circulating viruses is currently hampered by complex and expensive methods. Untargeted, metagenomic nanopore sequencing can provide genomic information to identify pathogens, prepare for or even prevent outbreaks. SMART (Switching Mechanism at the 5′ end of RNA Template) is a popular approach for RNA-Seq but most current methods rely on oligo-dT priming to target polyadenylated mRNA molecules. We have developed two random primed SMART-Seq approaches, a sequencing agnostic approach ‘SMART-9N’ and a version compatible rapid adapters available from Oxford Nanopore Technologies ‘Rapid SMART-9N’. The methods were developed using viral isolates, clinical samples, and compared to a gold-standard amplicon-based method. From a Zika virus isolate the SMART-9N approach recovered 10kb of the 10.8kb RNA genome in a single nanopore read. We also obtained full genome coverage at a high depth coverage using the Rapid SMART-9N, which takes only 10 minutes and costs up to 45% less than other methods. We found the limits of detection of these methods to be 6 focus forming units (FFU)/mL with 99.02% and 87.58% genome coverage for SMART-9N and Rapid SMART-9N respectively. Yellow fever virus plasma samples and SARS-CoV-2 nasopharyngeal samples previously confirmed by RT-qPCR with a broad range of Ct-values were selected for validation. Both methods produced greater genome coverage when compared to the multiplex PCR approach and we obtained the longest single read of this study (18.5 kb) with a SARS-CoV-2 clinical sample, 60% of the virus genome using the Rapid SMART-9N method. This work demonstrates that SMART-9N and Rapid SMART-9N are sensitive, low input, and long-read compatible alternatives for RNA virus detection and genome sequencing and Rapid SMART-9N improves the cost, time, and complexity of laboratory work.
Recognition of Trypanosoma cruzi epitopes by IgG of benznidazole treated Chagas disease patients
(2021) CARNERO, Luis Antonio Rodriguez; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; SABINO, Ester Cerdeira; NETO, Edecio Cunha; GIORDANO, Ricardo Jose
Therapeutic neutralizing monoclonal antibody administration protects against lethal yellow fever infection
(2023) RUST, Lauren N.; RICCIARDI, Michael J.; PEDRENO-LOPEZ, Nuria; YUSOVA, Sofiya; BISWAS, Sreya; FISCHER, Miranda; WEBB, Gabriela M.; GONZALEZ-NIETO, Lucas; VOIGT, Thomas B.; LOUW, Johan J.; LAURINO, Fernanda D.; DIBELLO, John R.; RAUE, Hans-Peter; RAPHAEL, Lidiane M. S.; YRIZARRY-MEDINA, Aaron; ROSEN, Brandon C.; AGNOR, Rebecca; GAO, Lina; LABRIOLA, Caralyn; AXTHELM, Michael D. V. M.; SMEDLEY, Jeremy; JULANDER, Justin G.; BONALDO, Myrna C.; WALKER, Laura M.; MESSAOUDI, Ilhem; SLIFKA, Mark K.; BURTON, Dennis R.; KALLAS, Esper G.; SACHA, Jonah B.; WATKINS, David I.; BURWITZ, Benjamin J.
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
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.
Encephalopathy Caused by Human Parvovirus B19 Genotype 1 Associated with Haemophilus influenzae Meningitis in a Newborn
(2023) FERREIRA, Noely Evangelista; COSTA, Antonio C. da; KALLAS, Esper G.; SILVEIRA, Cassia G. T.; OLIVEIRA, Ana Carolina S. de; HONORATO, Layla; PAIAO, Heuder G. O.; LIMA, Silvia H.; VASCONCELOS, Dewton de M.; CORTES, Marina F.; COSTA, Silvia F.; MENDOZA, Tania R. T.; GOMES, Helio R.; WITKIN, Steven S.; MENDES-CORREA, Maria C.
Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to Sao Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology.
HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing
(2023) LYONS, Danielle E.; KUMAR, Priti; ROAN, Nadia R.; DEFECHEREUX, Patricia A.; FESCHOTTE, Cedric; LANGE, Ulrike C.; MURTHY, Niren; SAMESHIMA, Pauline; VERDIN, Eric; AKE, Julie A.; PARSONS, Matthew S.; NATH, Avindra; GIANELLA, Sara; SMITH, Davey M.; KALLAS, Esper G.; VILLA, Thomas J.; STRANGE, Richard; MWESIGWA, Betty; O'BRIEN, Robert L. Furler; NIXON, Douglas F.; NDHLOVU, Lishomwa C.; VALENTE, Susana T.; OTT, Melanie
Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel ""block-lock-stop"" approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.