LUCIANA PARENTE COSTA SEGURO
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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conferenceObject CLINICAL AND SEROLOGICAL COMPARATIVE ANALYSIS OF SYSTEMIC SCLEROSIS WITH OR WITHOUT OVERLAP SYNDROMES IN A LARGE BRAZILIAN COHORT(2014) SILVA, C. M.; PASOTO, S. G.; VIANA, V. S.; SEGURO, L. P. C.; ANDRADE, D. C. O.; BONFA, E.; SAMPAIO-BARROS, P. D.article 4 Citação(ões) na Scopus Hypomagnesaemia and hypocalcaemia in a patient with systemic sclerosis: role of proton pump inhibitors(2014) PEREZ, M. O.; NEVES, E. F. V.; BORTOLAI, C. B. C.; SAMPAIO-BARROS, P. D.; ANDRADE, D. C. O.; SEGURO, L. P. C.Proton pump inhibitors (PPI) are widely used in patients with systemic sclerosis (SSc) due to the chronic gastroesophageal reflux. The authors report a female patient with a 9-year history of SSc and long-term use of omeprazole, who complained of paresthesia and asthenia for 12 months. Physical examination revealed clinical signs of hypocalcaemia confirmed by laboratory tests that also showed hypomagnesaemia. After exclusion of possible causes, hypomagnesaemia secondary to PPI was diagnosed and omeprazole was replaced by a histamine H2-receptor antagonist: ranitidine. Despite continuous magnesium supplementation, the reintroduction of PPI at a lower dose due to worsening of dyspeptic symptoms led to recurrence of hypomagnesaemia. After definitive suspension of PPI, reintroduction of ranitidine and optimisation of anti-reflux environmental measures, the patient stabilised. In conclusion, SSc patients using PPIs should have their magnesium and calcium serum levels measured periodically, and non-specific symptoms such as asthenia, generalised paresthesia or life-threatening manifestations (seizures, arrhythmias) should not be neglected.- CLINICAL AND SEROLOGICAL COMPARATIVE ANALYSIS OF SYSTEMIC SCLEROSIS WITH OR WITHOUT OVERLAP SYNDROMES IN A LARGE BRAZILIAN COHORT(2014) SILVA, C. M.; VIANA, V. S.; PASOTO, S. G.; SEGURO, L. P.; ANDRADE, D. C. O.; BONFA, E.; SAMOIO-BARROS, P. D.
- Immunogenicity and safety of two doses of the CoronaVac SARS-CoV-2 vaccine in SARS-CoV-2 seropositive and seronegative patients with autoimmune rheumatic diseases in Brazil: a subgroup analysis of a phase 4 prospective study(2022) AIKAWA, Nadia E.; KUPA, Leonard V. K.; PASOTO, Sandra G.; MEDEIROS-RIBEIRO, Ana C.; YUKI, Emily F. N.; SAAD, Carla G. S.; PEDROSA, Tatiana; FULLER, Ricardo; SHINJO, Samuel K.; SAMPAIO-BARROS, Percival D.; ANDRADE, Danieli C. O.; PEREIRA, Rosa M. R.; SEGURO, Luciana P. C.; VALIM, Juliana M. L.; WARIDEL, Filipe; SARTORI, Ana Marli C.; DUARTE, Alberto J. S.; ANTONANGELO, Leila; SABINO, Ester C.; MENEZES, Paulo Rossi; KALLAS, Esper G.; SILVA, Clovis A.; BONFA, EloisaBackground We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. Methods CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clinicas, Faculdade de Medicina da Universidade de Sao Paulo) in Sao Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 mu g in 0middot5 mL of beta-propiolactone inactivated SARSCoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15middot0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of >= 30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARSCoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. Findings Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38-56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52middot3 [95% CI 42middot9-63middot9] at day 0 vs 128middot9 [105middot6-157middot4] at day 28; seropositive controls 53middot3 [45middot4-62middot5] at day 0 vs 202middot0 [174middot8-233middot4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39-83] at day 0 vs 82% [54-96] at day 28; seropositive controls 58% [41-79] at day 0 vs 92% [79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137middot1 [116middot2-161middot9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188middot6 [167middot4-212middot6] and neutralising antibody activity was 92% [75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2middot3 (95% CI 2middot2-2middot3) at day 0, 5middot7 (5middot1-6middot4) at day 28, and 29middot6 (26middot4-33middot3) at day 69, and in seronegative controls were 2middot3 (2middot1-2middot5) at day 0, 10middot6 (8middot7-13middot1) at day 28, and 71middot7 (63middot5-81middot0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. Interpretation By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients.
- Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients(2022) SILVA, Clovis A.; MEDEIROS-RIBEIRO, Ana C.; KUPA, Leonard V. K.; YUKI, Emily F. N.; PASOTO, Sandra G.; SAAD, Carla G. S.; FUSCO, Solange R. G.; PEREIRA, Rosa M. R.; SHINJO, Samuel K.; HALPERN, Ari S. R.; BORBA, Eduardo F.; SOUZA, Fernando H. C.; GUEDES, Lissiane K. N.; MIOSSI, Renata; BONFIGLIOLI, Karina R.; DOMICIANO, Diogo S.; SHIMABUCO, Andrea Y.; ANDRADE, Danieli C. O.; SEGURO, Luciana P. C.; FULLER, Ricardo; SAMPAIO-BARROS, Percival D.; ASSAD, Ana P. L.; MORAES, Julio C. B.; GOLDENSTEIN-SCHAINBERG, Claudia; GIARDINI, Henrique A. M.; SILVA, Henrique C.; MARTINS, Victor A. O.; VILLAMARIN, Lorena E. B.; NOVELLINO, Renata S.; SALES, Lucas P.; ARAUJO, Carlo S. R.; SILVA, Matheus S. R.; FILHO, Dilson M. N.; LOPES, Marta H.; DUARTE, Alberto J. S.; KALLAS, Esper G.; AIKAWA, Nadia E.; BONFA, EloisaCharacterising the response to SARS-CoV-2 post vaccination is critical in the appraisement of the induced immune response, performance and protective potential. Here the authors present data from a phase 4 clinical trial in autoimmune rheumatic disease patients 6 months post second dose of Sinovac-CoronaVac inactivated vaccine that show a marked reduction in antibody particularly in males or those under treatment with immune targeting therapies but saw no rise in COVID-19 disease. The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2(nd) dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p < 0.001) during the six-month follow up and 20% and 51% in controls (p < 0.001), respectively. Neutralizing antibodies positivity and percent inhibition declines 41% and 54% in patients (p < 0.001) and 39.7% and 47% in controls (p < 0.001). Multivariate logistic regression analysis show males (OR = 0.56;95% CI0.40-0.79), prednisone (OR = 0.56; 95% CI0.41-0.76), anti-TNF (OR = 0.66;95% CI0.45-0.96), abatacept (OR = 0.29; 95% CI0.15-0.56) and rituximab (OR = 0.32;95% CI0.11-0.90) associate with a substantial reduction in IgG response at day 210 in patients. Although cellular immunity was not assessed, a decrease of COVID-19 cases (from 27.5 to 8.1/100 person-years; p < 0.001) is observed despite the concomitant emergence and spread of the Delta variant. Altogether we show a reduction in immunity 6-months of Sinovac-CoronaVac 2nd dose, particularly in males and those under immunosuppressives therapies, without a concomitant rise in COVID-19 cases. (CoronavRheum clinicaltrials.gov:NCT04754698).
- Immunogenicity, safety, and antiphospholipid antibodies after SARS-CoV-2 vaccine in patients with primary antiphospholipid syndrome(2022) SIGNORELLI, Flavio; BALBI, Gustavo Guimaraes Moreira; AIKAWA, Nadia E.; SILVA, Clovis A.; KUPA, Leonard de Vinci Kanda; MEDEIROS-RIBEIRO, Ana C.; YUKI, Emily F. N.; PASOTO, Sandra G.; SAAD, Carla G. S.; BORBA, Eduardo F.; SEGURO, Luciana Parente Costa; PEDROSA, Tatiana; OLIVEIRA, Vitor Antonio de Angeli; COSTA, Ana Luisa Cerqueira de Sant'Ana; RIBEIRO, Carolina T.; SANTOS, Roseli Eliana Beseggio; ANDRADE, Danieli Castro Oliveira; BONFA, EloisaObjective Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). Recent reports of thrombosis associated with adenovirus-based vaccines raised concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger clotting complications. Our objectives were to assess immunogenicity, safety, and aPL production in PAPS patients, after vaccinating with Sinovac-CoronaVac, an inactivated virus vaccine against COVID-19. Methods This prospective controlled phase-4 study of PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69 in naive participants. Safety and aPL production were also assessed. Results We included 44 PAPS patients (31 naive) and 132 CG (108 naive) with comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092), as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity (64.3% vs. 60.9%, p=0.689). Thrombotic events up to 6 months or other moderate/severe side effects were not observed. PAPS patients remained with stable aPL levels throughout the study at D0 vs. D28 vs. D69: anticardiolipin (aCL) IgG (p=0.058) and IgM (p=0.091); anti-beta-2 glycoprotein I (a beta 2GPI) IgG (p=0.513) and IgM (p=0.468). Conclusion We provided novel evidence that Sinovac-CoronaVac has high immunogenicity and safety profile in PAPS. Furthermore, Sinovac-CoronaVac did not trigger thrombosis nor induced changes in aPL production.
article 0 Citação(ões) na Scopus Kidney biopsy is mandatory in cases of silent arterial hypertension in scleroderma renal crisis: a case report(2014) KOBAYASHI, C. B. C.; BENTO, R. H.; MALHEIROS, D. M. A. C.; ANDRADE, D.; SEGURO, L. C. P.; SAMPAIO-BARROS, P. D.- ABO blood group in primary antiphospholipid syndrome: influence in the site of thrombosis?(2015) NASCIMENTO, Natalia Mastantuono; BYDLOWSKI, Sergio Paulo; SOARES, Rosangela Paula Silva; ANDRADE, Danieli Castro Oliveira de; BONFA, Eloisa; SEGURO, Luciana Parente Costa; BORBA, Eduardo FerreiraAntiphospholipid syndrome (APS) is characterized by vascular thrombosis and/or obstetric complications associated with presence of antiphospholipid antibodies (aPL) but additional factors would also induce thrombosis. ABO (H) blood groups are known to be closely related to thrombosis, especially non-O blood type with venous events. The aim of this study was to investigate possible role of ABO (H) blood types in the thrombotic events in primary APS (PAPS). Seventy PAPS patients were selected for the study and were divided according to ABO blood group in: O PAPS (n = 26) and non-O PAPS (n = 44). ABO blood group phenotyping was performed by indirect technique. aPL anticardiolipin (aCL) and anti-beta eta2 glycoprotein-1 (a beta 2GPI) and the concentrations and activities of von Willebrand factor (VWF) were measured with ELISA. Lupus anticoagulant (LA) was detected by coagulation assays. A significant higher frequency of venous events was observed in non-O PAPS group (72.7 vs. 46.2 %, p = 0.040). In contrast, the frequency of arterial events was significantly higher in the O PAPS compared to the non-O PAPS group (69.2 vs. 36.4 %, respectively; p = 0.013). Frequencies of aCL, LA, a beta 2GPI and triple aPL positivity were similar in both groups (p > 0.05). VWF antigen (75.54 +/- A 8.68 vs. 79.51 +/- A 7.07 IU/dl, p = 0.041) and activity (70.23 +/- A 11.96 vs. 77.92 +/- A 13.67 %, p = 0.020) were decreased in O PAPS compared to non-O blood group. VWF:CB/VWF:Ag ratio was similar among groups (p > 0.05). This is the first report that confirms the role of ABO blood system in thrombosis of PAPS and suggests that non-O blood group was related with venous events and O blood group with arterial thrombosis.
conferenceObject ENVIRONMENTAL FACTORS AND INDUCTION OF SYSTEMIC SCLEROSIS: ANALYSIS OF 211 CONSECUTIVE PATIENTS(2014) SAMPAIO-BARROS, P.; AQUILA, L.; MEDEIROS, A. C.; SEGURO, L.; ANDRADE, D.conferenceObject INFLUENCE OF GENDER, ETHNICITY AND AGE AT ONSET IN THE CLINICAL PRESENTATION OF SYSTEMIC SCLEROSIS IN A LARGE BRAZILIAN COHORT OF 1017 PATIENTS(2014) SAMPAIO-BARROS, P.; MARANGONI, R.; ROCHA, L.; BORTOLUZZO, A.; SEGURO, L.; RIO, A. P. Del; ANDRADE, D.; NASCIMENTO, I.; FOELKEL, A. L.; MARQUES-NETO, J. F.