CLEONICE BUENO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
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 Pandemic Influenza Immunization in Primary Antiphospholipid Syndrome (PAPS): A Trigger to Autoantibody Production?(2012) MEDEIROS, Danielle M.; BUENO, Cleonice; RIBEIRO, Ana Cristina M.; CALICH, Ana L. G.; BONFIGLIOLI, Karina Rossi; VIANA, Vilma S.; CARVALHO, Jozelio F.; SILVA, Clovis Artur; BONFA, EloisaBackground/Purpose: There are scarce data suggesting that pan-demic influenza vaccination may induce antiphospholipid (APL) autoan- tibodies in inflammatory rheumatic diseases, particularly in systemic lupus erythematosus patients. However, there is no study evaluating the APL autoantibodies induction in primary antiphospholipid syndrome (PAPS) patients. The objective was to perform short and long-term evaluations of a large panel of APL autoantibodies following pandemic influenza A/H1N1 non-adjuvant vaccine in PAPS patients and healthy controls. Lupus specific antibodies were also investigated in these patients. Methods: Forty-five PAPS patients (Sapporo criteria) and 33 healthy controls were vaccinated with monovalent, inactivated H1N1 vaccine (Butantan Institute/Sanofi Pasteur, São Paulo, Brazil). They were prospec-tively assessed at pre-vaccination, 3 weeks and 6 months after vaccination. APL autoantibodies were determined by an enzyme-linked immunosor-bent assay (ELISA) and included: anti-cardiolipin (aCL) IgG/IgM and anti-β2GPI IgG/IgM antibodies (Inova Diagnostics, USA); anti-annexin V IgG/IgM, anti-phosphatidyl serine IgG/IgM and anti-prothrombin IgG/IgM (Orgentec Diagnostica, Germany). Anti-Sm was determined by ELISA (Inova Diagnostics, USA) and anti-dsDNA by indirect immun-fluorescence. Arterial and venous thromboses were also clinically assessed. The statistical analyses were carried out with qui square test, McNemar s test and one-way repeated measures analysis of variance (ANOVA). Results: Pre-vaccination frequency of at least one APL antibody was significantly higher in PAPS patients compared to controls (58% vs. 21%, p=0.003). The overall frequencies of APL antibody at pre-vaccination, 3 weeks and 6 months after immunization remained unchanged in patients (p=0.89) and controls (p=0.83). Further analysis of each evaluated antibody in PAPS revealed that their percentages at pre-vaccination and after 3 weeks and 6 months were also comparable (p>0.05): aCL IgG (42%, 38% and 42%), aCL IgM (22%, 20% and 24%), anti-β2GPI IgG (22%, 22% and 20%), anti-β2GPI IgM (15%, 15% and 18%), anti- annexin V IgG (4.5%, 4.5% and 2.5%), anti-annexin V IgM (uniformly negative), anti-phosphatidyl serine IgG (38%, 35% and 38%), anti- phosphatidyl serine IgM (15%, 13% and 13%), anti-prothrombin IgG (20%, 15% and 18%) and anti-prothrombin IgM (2.5%, 2.5% and 2.5%). The same pattern was observed for the control group (p>0.05). At 3 weeks, 2 PAPS patients developed a new but transient APL anti-body (moderate titer aCL IgG and IgM) whereas at 6 months, new APL antibodies were observed in 6 PAPS patients: 3 moderate titer aCL IgM, 1 moderate anti-β2GPI IgM, 1 low anti-phosphatidyl serine IgG and 1 low anti-prothrombin IgG. Fluctuations of antibody levels were not detected for any evaluated antibody (p>0.05). Of note, anti-Sm and anti-dsDNA autoantibodies were consistently negative during all evaluations. No new arterial or venous thrombosis events occurred during the study period. Conclusion: This was the first study to demonstrate that pandemic non-adjuvant influenza A/H1N1 in PAPS patients does not trigger a change in APL antibody profile or induce lupus specific autoantibodies.- Effective seroconversion and safety following the pandemic influenza vaccination (anti-H1N1) in patients with juvenile idiopathic arthritis(2013) AIKAWA, N. E.; CAMPOS, L. M. A.; GOLDENSTEIN-SCHAINBERG, C.; SAAD, C. G. S.; RIBEIRO, A. C.; BUENO, C.; PRECIOSO, A. R.; TIMENETSKY, MdoC; SILVA, C. A. A.; BONFA, E.Objectives: To assess the vaccine response in juvenile idiopathic arthritis (JIA) as an extension of previous observation of immunogenicity and safety of a non-adjuvanted influenza A H1N1/2009 vaccine in a large population of juvenile rheumatic diseases. Moreover, to assess the possible influence of demographic data, disease subtypes, disease activity, and treatment on immunogenicity and the potential deleterious effect of the vaccine in the disease itself, particularly in the number of arthritis and inflammatory markers. Methods: A total of 95 patients with JIA and 91 healthy controls were evaluated before and 21 days after vaccination, and serology for anti-H1N1 was performed by haemagglutination inhibition assay (HIA). Patient and physician visual analogue scales (VAS), Childhood Health Assessment Questionnaire (CHAQ), number of active joints, acute phase reactants, and treatments were evaluated before and after vaccination. Adverse events were also reported. Results: JIA patients and controls were comparable regarding mean current age (14.9 +/- 3.2 vs. 14.6 +/- 3.7 years, p = 0.182). After vaccination, the seroconversion rate was significantly lower in JIA patients compared to controls (83.2% vs. 95.6%, p = 0.008), particularly in the polyarticular subtype (80% vs. 95.6%, p = 0.0098). Of note, JIA subtypes, number of active joints, acute phase reactants, CHAQ, patient and physician VAS, and use of disease-modifying anti-rheumatic drugs (DMARDs)/immunosuppressive drugs were similar between seroconverted and non-seroconverted patients (p > 0.05). Regarding vaccine safety, no deterioration was observed in the number of active joints and acute phase reactants during the study period. Conclusion: Influenza A H1N1/2009 vaccination in JIA induces a lower but effective protective antibody response probably independent of disease parameters and treatment with an adequate disease safety profile.
- Pandemic influenza immunization in primary antiphospholipid syndrome (PAPS): a trigger to thrombosis and autoantibody production?(2014) MEDEIROS, D. Martins de; SILVA, C. A.; BUENO, C.; RIBEIRO, A. C. Medeiros; VIANA, V. dos Santos T.; CARVALHO, J. Freire; BONFA, E.Objective The objective of this report is to conduct short- and long-term evaluation of a large panel of antiphospholipid (aPL) autoantibodies following pandemic influenza A/H1N1 non-adjuvant vaccine in primary antiphospholipid syndrome (PAPS) patients and healthy controls. Methods Forty-five PAPS and 33 healthy controls were immunized with H1N1 vaccine. They were prospectively assessed at pre-vaccination, and three weeks and six months after vaccination. aPL autoantibodies were determined by an enzyme-linked immunosorbent assay (ELISA) and included IgG/IgM: anticardiolipin (aCL), anti-beta2glycoprotein I (anti-2GPI); anti-annexin V, anti-phosphatidyl serine and anti-prothrombin antibodies. Anti-Sm was determined by ELISA and anti-double-stranded DNA (anti-dsDNA) by indirect immunofluorescence. Arterial and venous thrombosis were also clinically assessed. Results Pre-vaccination frequency of at least one aPL antibody was significantly higher in PAPS patients versus controls (58% vs. 24%, p=0.0052). The overall frequencies of aPL antibody at pre-vaccination, and three weeks and six months after immunization remained unchanged in patients (p=0.89) and controls (p=0.83). The frequency of each antibody specificity for patients and controls remained stable in the three evaluated periods (p>0.05). At three weeks, two PAPS patients developed a new but transient aPL antibody (aCL IgG and IgM), whereas at six months new aPL antibodies were observed in six PAPS patients and none had high titer. Anti-Sm and anti-dsDNA autoantibodies were uniformly negative and no new arterial or venous thrombosis were observed throughout the study. Conclusions This is the first study to demonstrate that pandemic influenza vaccine in PAPS patients does not trigger short- and long-term thrombosis or a significant production of aPL-related antibodies (ClinicalTrials.gov, #NCT01151644).
- Inactivated SARS-CoV-2 vaccine in primary Sjogren's syndrome: humoral response, safety, and effects on disease activity(2022) PASOTO, Sandra Gofinet; HALPERN, Ari Stiel Radu; GUEDES, Lissiane Karine Noronha; RIBEIRO, Ana Cristina Medeiros; YUKI, Emily Neves Figueiredo; SAAD, Carla Goncalves Schahin; SILVA, Clovis Artur Almeida da; KUPA, Leonard de Vinci Kanda; VILLAMARIN, Lorena Elizabeth Betancourt; MARTINS, Victor Adriano de Oliveira; MARTINS, Carolina Campagnoli Machado Freire; DEVEZA, Giordano Bruno Henriques; LEON, Elaine Pires; BUENO, Cleonice; PEDROSA, Tatiana Nascimento; SANTOS, Roseli Eliana Beseggio; SOARES, Renata; AIKAWA, Nadia Emi; BONFA, EloisaIntroduction There is no study specifically focused on SARS-CoV-2 vaccine in primary Sjogren's syndrome (pSS). Objectives To assess the immunogenicity, safety, possible effects on disease activity, and autoantibody profile of the Sinovac-CoronaVac vaccine in pSS. Methods Fifty-one pSS patients and 102 sex- and age-balanced controls without autoimmune diseases were included in a prospective phase 4 trial of the Sinovac-CoronaVac vaccine (two doses 28 days apart, D0/D28). Participants were assessed in three face-to-face visits (D0/D28 and six weeks after the 2nd dose (D69)) regarding adverse effects; clinical EULAR Sjogren's Syndrome Disease Activity Index (clinESSDAI); anti-SARS-CoV-2 S1/S2 IgG (seroconversion (SC) and geometric mean titers (GMT)); neutralizing antibodies (NAb); and pSS autoantibody profile. Results Patients and controls had comparable female sex frequency (98.0% vs. 98.0%, p= 1.000) and mean age (53.5 +11.7 vs. 53.4 +11.4 years, p= 0.924), respectively. On D69, pSS patients presented moderate SC (67.5% vs. 93.0%, p< 0.001) and GMT (22.5 (95% CI 14.6-34.5) vs. 59.6 (95% CI 51.1-69.4) AU/mL, p< 0.001) of anti-SARS-CoV-2 S1/S2 IgG but lower than controls, and also, moderate NAb frequency (52.5% vs. 73.3%, p= 0.021) but lower than controls. Median neutralizing activity on D69 was comparable in pSS (58.6% (IQR 43.7-63.6)) and controls (64% (IQR 46.4-81.1)) (p= 0.219). Adverse events were mild. clinESSDAI and anti-Ro(SS-A)/anti-La(SS-B) levels were stable throughout the study (p> 0.05). Conclusion Sinovac-CoronaVac vaccine is safe in pSS, without a deleterious impact on disease activity, and has a moderate short-term humoral response, though lower than controls. Thus, a booster dose needs to be studied in these patients.
- Short and long-term effects of pandemic unadjuvanted influenza A(H1N1)pdm09 vaccine on clinical manifestations and autoantibody profile in primary Sjogren's syndrome(2013) PASOTO, Sandra Gofinet; RIBEIRO, Ana Cristina; VIANA, Vilma Santos Trindade; LEON, Elaine Pires; BUENO, Cleonice; LEVY NETO, Mauricio; PRECIOSO, Alexander Roberto; TIMENETSKY, Maria do Carmo Sampaio Tavares; BONFA, EloisaDespite WHO recommendations about the A/Califomia/7/2009/H1N1-like virus vaccination, studies evaluating its possible influence on clinical manifestations and autoantibody profile in primary Sjogren's syndrome (SS) are scarce. The aim of this study was to evaluate the possible influence of the unadjuvanted A/Califomia/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS in the short/long-term. Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 healthy controls with comparable mean age and gender were evaluated before and 21-days after this vaccination regarding seroprotection/seroconversion, factor increase in geometric mean titer (FI-GMT) and side effects. New onset of disease flares and autoantibody profile [antinuclear antibodies, anti-dsDNA, anti-Ro(SSA)/La(SSB), anti-RNP/anti-Sm, rheumatoid factor, anti-alpha-fodrin, anticardiolipin and anti-beta2-glycoprotein-I] were assessed before, 21-days and 1-year after vaccination. Patients and controls had similar rates of seroconversion (77.8 vs. 69.4%, p = 0.42), seroprotection (83.3 vs. 72.2%, p = 0.26) and FI-GMT (p = 0.85). Disease duration, prednisone (2.1 +/- 4.9 mg/day), methotrexate and azathioprine did not affect seroconversion (p > 0.05). Regarding short-term, no change in the frequency or levels of autoantibodies was observed (p > 0.05) and only mild side effects were reported in comparable rates to controls (p > 0.05). During 1-year follow-up, the frequency of new disease flares was similar to the previous year (11 vs. 19%, p = 0.51), and four patients developed positivity to one of the following specificities: anti-Ro(SSA)/anti-La/(SSB), anti-alpha-fodrin, or IgM anticardiolipin. None developed specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SSA (p = 0.0001) and anti-La/SSB (p = 0.002) was detected after 1-year with no change in the other autoantibodies. This is the first study indicating that influenza A(H1N1)pdm09 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.
conferenceObject Long-Term Changes in Autoantibody Profile After Pandemic Unadjuvanted Influenza A/H1N1 Vaccine in Sjogren's Syndrome(2012) PASOTO, Sandra G.; RIBEIRO, Ana C.; VIANA, Vilma S. T.; LEON, Elaine P.; BUENO, Cleonice; NETO, Mauricio Levy; PRECIOSO, Alexander R.; TIMENETSKY, Maria do Carmo S.; BONFA, EloisaBackground/Purpose: Despite WHO recommendations about the A/California/7/2009/H1N1-like virus vaccination, there are no studies evalu- ating its possible influence on clinical manifestations and autoantibody profile in (primary) Sjögren’s syndrome (SS). Objectives: To evaluate short/long-term effect of influenza A/California/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS. Methods: Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 gender-, age-, matched-healthy controls were evaluated before and 21-days after vaccination with unadjuvanted influenza A/H1N1-like virus regarding seroprotection/seroconversion, factor increase in geometric mean titre (FI-GMT) and side effects. New onset of parotiditis, arthritis, vasculitis, pneumonitis or neurological disorders and autoantibody profile [antinuclear antibodies (ANA), rheumatoid factor (RF), anti-dsDNA, anti-Ro(SS-A)/La(SS-B), anti-alpha-fodrin, anti-RNP, anti-Sm and anticar-diolipin] were assessed before, 21-days and 1-year after vaccination. Results: Patients and controls had similar rates of seroconversion (78 vs. 69%, p=0.42), seroprotection (83 vs. 72%, p=0.26) and FI-GMT (p=0.85). Pre-vaccination evaluation revealed that disease duration, glucocorticoid (mean dose 10.15.1 mg/day), methotrexate (up to 17.5 mg/week) or azathioprine (up to 100 mg/day) did not affect seroconversion (p> 0.05). Regarding short-term analysis, no change in the frequency or levels of autoantibodies was observed (p>0.05) and only mild side effects were observed in comparable rates to controls (p> 0.05). At 1-year follow-up, the rate of new disease flares was similar to the previous year (11 vs. 19%, p 0.51) and four seroconverted patients developed positivity to one of the following specificities: anti-Ro/SS-A, anti-La/SS-B, anti-alpha-fodrin, or IgM anticardiolipin. None developed other specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SS-A (p< 0.0001) and anti-La/SS-B (p< 0.002) was detected after 1-year with no change in the other autoantibodies. Conclusion: This is the first study to indicate that influenza A/H1N1 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.conferenceObject Interstitial Lung Abnormalities in Rheumatoid Arthritis Patients: Identifying Associated Risk Factors(2019) BONFIGLIOLI, Karina; SAWAMURA, Marcio; NAKAGAWA, Renato; ARIMURA, Fabio; RANGEL, Diana; BUENO, Cleonice; RIBEIRO, Ana Cristina de Medeiros; CARVALHO, Carlos; BONFA, Eloisa; KAIRALLA, Ronaldo; KAWANO-DOURADO, Leticia