ADRIANA CORACINI TONACIO DE PROENCA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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- Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus(2023) AIKAWA, Nadia Emi; BORBA, Eduardo Ferreira; BALBI, Verena Andrade; SALLUM, Adriana Maluf Elias; BUSCATTI, Izabel Mantovani; CAMPOS, Lucia Maria Arruda; KOZU, Katia Tomie; GARCIA, Cristiana Couto; CAPAO, Artur Silva Vidal; PROENCA, Adriana Coracini Tonacio de; LEON, Elaine Pires; DUARTE, Alberto Jose da Silva; LOPES, Marta Heloisa; SILVA, Clovis Artur; BONFA, EloisaIntroduction Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature.Objective To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE.Methods 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated.Results JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI >= 4 (p = 0.713), as well as between patients with and without current use of prednisone (p = 0.420), azathioprine (p = 1.0), mycophenolate mofetil (p = 0.185), and methotrexate (p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups (p > 0.05).Conclusion This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. (www.clinicaltrials.gov, NCT03540823).
- Influenza A/Singapore (H3N2) component vaccine in systemic lupus erythematosus: A distinct pattern of immunogenicity(2021) FORMIGA, Francisco Fellipe Claudino; SILVA, Clovis Artur; PEDROSA, Tatiana do Nascimento; AIKAWA, Nadia Emi; PASOTO, Sandra Gofinet; GARCIA, Cristiana Couto; CAPAO, Artur Silva Vidal; MARTINS, Victor Adriano de Oliveira; PROENCA, Adriana Coracini Tonacio de; FULLER, Ricardo; YUKI, Emily Figueiredo Neves; VENDRAMINI, Margarete Borges Galhardo; ROSARIO, Debora Cordeiro do; BRANDAO, Leticia Maria Kolachinski Raposo; SARTORI, Ana Marli Christovam; ANTONANGELO, Leila; BONFA, Eloisa; BORBA, Eduardo FerreiraIntroduction Influenza A (H3N2) virus is the most important cause of seasonal influenza morbidity and mortality in the last 50 years, surpassing the impact of H1N1. Data assessing immunogenicity and safety of this virus component are lacking in systemic lupus erythematosus (SLE) and restricted to small reports with other H3N2 strains. Objective This study aims to evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in SLE. Methods 81 consecutive SLE patients and 81 age- and sex-matched healthy controls (HC) were vaccinated with the influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers(GMT), and factor increase in GMT(FI-GMT) and adverse events were assessed before and 4 weeks post-vaccination. Disease activity and therapies were also evaluated. Results Before immunization, SLE and HC groups had high SP rates (89% vs 77%, p = 0.061) and elevated GMT titer with higher levels in SLE (129.1(104.1-154.1) vs 54.8(45.0-64.6), p < 0.001). Frequency of two previous years' influenza vaccination was high and comparable in SLE and HC (89% vs 90%, p = 1.000). Four weeks post-vaccination, median GMT increased for both groups and remained higher in SLE compared to HC (239.9(189.5-290.4) vs 94.5(72.6-116.4), p < 0.0001) with a comparable FI-GMT (2.3(1.8-2.9) vs 1.9(1.5-2.3), p = 0.051). SC rates were low and comparable for both groups (16% vs 11%, respectively, p = 0.974). Disease activity scores remained stable throughout the study (p = 1.000) and severe adverse events were not identified. Conclusion Influenza A/Singapore (H3N2) vaccine has an adequate safety profile. The distinct immunogenicity pattern from other influenza A components characterized by a remarkably high pre- and post-vaccination SP rate and high GMT levels may be associated with previous influenza A vaccination. (, NCT03540823).
- Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases(2021) TONACIO, Adriana Coracini; PEDROSA, Tatiana do Nascimento; BORBA, Eduardo Ferreira; AIKAWA, Nadia Emi; PASOTO, Sandra Gofinet; FERREIRA FILHO, Julio Cesar Rente; BARROS, Marilia Mantovani Sampaio; LEON, Elaine Pires; LOMBARDI, Suzete Cleusa Ferreira Spina; MENDRONE JUNIOR, Alfredo; AZEVEDO, Adriana de Souza; SCHWARCZ, Waleska Dias; FULLER, Ricardo; YUKI, Emily Figueiredo Neves; LOPES, Michelle Remiao Ugolini; PEREIRA, Rosa Maria Rodrigues; BARROS, Percival Degrava Sampaio; ANDRADE, Danieli Castro Oliveira de; MEDEIROS-RIBEIRO, Ana Cristina de; MORAES, Julio Cesar Bertacini de; SHINJO, Samuel Katsuyuki; MIOSSI, Renata; DUARTE, Alberto Jose da Silva; LOPES, Marta Heloisa; KALLAS, Esper Georges; SILVA, Clovis Artur Almeida da; BONFA, EloisaBackground Brazil faced a yellow fever(YF) outbreak in 2016-2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. Objective This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. Methods and Results A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3-1292.2) vs.731 (95%CI 593.6-900.2), p< 0.001] were significantly lower in ARD compared to controls. A lower positivity rate of viremia was also identified for ARD patients compared to controls at D5 (53%vs.70%, p = 0.005) and the levels persisted in D10 for patients and reduced for controls(51%vs.19%, p = 0.0001). The viremia was the only variable associated with seroconvertion. No serious adverse events were reported. ARD disease activity parameters remained stable at D30(p>0.05). Conclusion Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(> 80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas.
- MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection(2018) PAQUIN-PROULX, Dominic; AVELINO-SILVA, Vivian I.; SANTOS, Bianca A. N.; BARSOTTI, Nathalia Silveira; SIROMA, Fabiana; RAMOS, Jessica Fernandes; TONACIO, Adriana Coracini; SONG, Alice; MAESTRI, Alvino; CERQUEIRA, Natalia Barros; FELIX, Alvina Clara; LEVI, Jose Eduardo; GREENSPUN, Benjamin C.; ROUGVIE, Miguel de Mulder; ROSENBERG, Michael G.; NIXON, Douglas F.; KALLAS, Esper G.Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are pre-dominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barre A syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFN gamma response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFN gamma in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.
- Yellow fever vaccination in Brazil: Short-term safety and immunogenicity in juvenile autoimmune rheumatic diseases(2022) AIKAWA, Nadia Emi; BALBI, Verena Andrade; BORBA, Eduardo Ferreira; TONACIO, Adriana Coracini; SALLUM, Adriana Maluf Elias; CAMPOS, Lucia Maria Arruda; KOZU, Katia Tomie; VENDRAMINI, Margarete Borges; FONTOURA, Nicole; AZEVEDO, Adriana de Souza; SCHWARCZ, Waleska Dias; SARTORI, Ana Marli Christovam; ANTONANGELO, Leila; SILVA, Clovis Artur; BONFA, EloisaYellow fever vaccine (YFV) is a live attenuated vaccine usually contraindicated for juvenile autoimmune rheumatic disease (JARD) patients. During the recent epidemic in Sao Paulo-Brazil, YFV was indicated for patients under low immunosuppression. Thirty JARD patients with inactive diseases undergoing low immunosuppression and 30 healthy controls (HC) were vaccinated with a fractional dose 17DD YFV (similar to 5495 IU) and evaluated 30 days later. JARD patients and controls had comparable median age (12.4 vs. 12 years, p = 0.250). Disease parameters remained stable 30 days after 17DD YFV (p > 0.05) and only mild adverse events were reported in both groups (p > 0.05). JARD and HC had similar seroprotection [93% vs. 100%;p = 0.49], seroconversion rates [96% vs. 100%;p = 0.489], and GMT [1249 vs.1293; p = 0.821]. Both groups had similar white-blood-cells kinetics with transient decreases in lymphocytes at D5 and neutrophils at D10, followed by full recovery at D30 (P < 0.05). In conclusion, 17DD YFV was safe and immunogenic in JARD. This study may contribute to recommendations for patients living/travelling to endemic areas. (C) 2021 The Authors.
- Trauma is associated with a better prognosis in intensive care patients with Acinetobacter infections(2014) TONACIO, A. C.; OLIVEIRA, M. S.; MALBOUISSON, L. M. S.; LEVIN, A. S.Acinetobacter baumannii has emerged as a common cause of infection in war-related trauma, civilian trauma and other surgical emergencies. The aim of this study was to determine prognostic factors especially trauma, in critically ill surgical patients with Acinetobacter spp. infection in a reference emergency ICU. A retrospective review of medical records was conducted for all patients admitted to the ICU who developed Acinetobacter spp. infection from January 2007 to December 2009. Bivariate and multivariate analyses were made for 36 patients. The end-point analyzed was the in-hospital mortality. The initial analysis revealed a majority of young (43.6 years +/- A 17.1) men (92 %), trauma victims (78 %) and an in-hospital mortality of 30 %. Patients who had not suffered trauma presented with other surgical conditions and were on average older than trauma patients (57 +/- A 12 versus 40 +/- A 16 years). The overall APACHE II score average was 15.3. The ventilator-associated pneumonia was the main Acinetobacter infection diagnosed. In bivariate analysis lower Glasgow coma scale (p = 0.01) was associated with increased chance of death and being victim of trauma was a protecting factor (OR: 0.16; 95 % CI: 0.03-0.89). Receiving adequate treatment made no difference to outcome (OR: 0.55; 95 % CI: 0.05-3.15). Multivariate analysis showed that only the presence of trauma was independently associated with prognosis and was a protecting factor. Trauma was a marker of good prognosis in emergency ICU patients with Acinetobacter spp. infection.
- Neisseria gonorrhoeae arthritis in a patient with systemic lupus: resistance and virulence profiles(2023) TONACIO, Adriana Coracini; MARCHI, Ana Paula; BAZZO, Maria Luiza; LEMOS, Gabriela Takeshigue; BAMPI, Jose Victor Bortolotto; ESPINOZA, Evelyn Patricia Sanchez; DUARTE, Edson Luiz Tarsia; MARTINS, Roberta Cristina Ruedas; COSTA-LOURENCO, Ana Paula Ramalho da; OLIVEIRA, Vitor Falcao de; CORTES, Marina Farrel; SANTOS, Sania Alves dos; NETO, Lauro Vieira Perdigao; BONELLI, Raquel Regina; ELMORE, Maria Rita; ROSSI, Flavia; HUGHES, Gwenda; COSTA, Silvia FigueiredoIn this study, we describe a case report of gonococcal arthritis in a Systemic Lupus Erythematosus patient. Although several mechanisms favor disseminated gonococcal infection (DGI) in patients immunosup-pressed by SLE, this association is rarely reported in literature. We performed whole genome sequencing (WGS) of the etiologic agent involved and molecular analysis using a global collection of Neisseria gonorrhoeae strains. Ours is the only sample derived from synovial fluid identified in this collection, the others being from the usual anatomical sites. Antimicrobial susceptibility was determined by disk diffusion and Etest, and WGS was conducted to determine multilocus sequence typing profiles, group isolates based on core genome single nucleotide polymorphisms (SNP), and identify virulence genes and antimicrobial resistance determinants. The N. gonorrhoeae samples in the global collection were highly heterogeneous. The SNP tree had a total 19,532 SNPs in 320 samples. Our sample displayed resistance to ciprofloxacin (MIC = 2 mg/mL) and tetracycline (zone diameter = 0 mm) belonged to ST 1588 and was not closely related to any isolate in the global collection of N. gonorrhoeae strains. The isolate had genetic features related to beta-lactam, tetracycline and quinolone resistance. Seventy-one virulence genes were identified in our sample, belonging to the following classes: adherence, efflux pump, immune modulator, invasion, iron uptake, protease and stress adaptation. Moreover, no virulence genes for immune evasion and toxin were identified.(c) 2022 Institut Pasteur.
- Robust immunogenicity to the H3N2 component of influenza A vaccine in primary Sjogren syndrome(2023) PASOTO, Sandra Gofinet; BORBA, Eduardo Ferreira; FORMIGA, Francisco Fellipe Claudino; PEDROSA, Tatiana do Nascimento; AIKAWA, Nadia Emi; SIQUEIRA, Marilda Agudo Mendonca Teixeira de; CAPAO, Artur Silva Vidal; PROENCA, Adriana Coracini Tonacio de; FULLER, Ricardo; YUKI, Emily Figueiredo Neves; LEON, Elaine Pires; MARTINS, Victor Adriano de Oliveira; LOPES, Marta Heloisa; DUARTE, Alberto Jose da Silva; SILVA, Clovis Artur Almeida da; BONFA, EloisaIntroduction Influenza A (H3N2) virus is the major cause of morbidity/mortality due to seasonal influenza over 50 years. Data about the safety/immunogenicity of influenza A/Singapore (H3N2) vaccine are scarce in primary Sjogren syndrome (pSS). Methods Twenty-one consecutive pSS patients and 42 HC (healthy control individuals) were immunized with influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus. Rates of SP (seroprotection) and SC (seroconversion), GMT (geometric mean titers), FI-GMT (factor increase in GMT), ESSDAI (EULAR Sjogren's Syndrome Disease Activity Index), and adverse events were appraised before and 4 weeks post-vaccination. Results pSS and HC had similar mean age (51.2 +/- 14.2 vs. 50.6 +/- 12.1 years, p =0.886). Pre-vaccination SP rates were high in pSS and HC (90.5% vs. 71.4%, p =0.114), and GMT were higher in pSS [80.0 (52.4-160.0) vs. 40.0 (20.0-80.0), p =0.001]. The percentage of influenza vaccination in the preceding two years was elevated and similar in pSS and HC (94.1% vs. 94.6%, p = 1.000). GMT values augmented in both groups four weeks after vaccination and persisted higher in the first group [160.0 (80.0-320.0) vs. 80.0 (40.0-80.0), p< 0.001] with equivalent FI-GMT [1.4 (1.0-2.8) vs. 1.4 (1.0-2.0), p = 0.410]. Both groups had low and similar SC rates (19.0% vs. 9.5%, p = 0.423). ESSDAI values persisted steadily during the study (p = 0.313). No serious adverse events have occurred. Conclusion The novel demonstration that the influenza A/Singapore (H3N2) vaccine induces a different pattern of immunogenicity from other influenza A constituents in pSS, featured by a desirable high pre- and post-vaccination immunogenicity, is in line with reported differences in immune responses between strains in trivalent vaccines and may be related to pre-existing immunity. Clinicaltrials.gov: #NCT03540823.