ELAINE PIRES LEON
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, 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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Resultados de Busca
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conferenceObject Abatacept Related Infections: No Association with Gammaglobulin Reduction.(2014) DINIS, Valquiria; VIANA, Vilma S. T.; LEON, Elaine P.; SILVA, Clovis A.; SAAD, Carla G. S.; MORAES, Julio C. B.; BONFA, Eloisa; RIBEIRO, Ana C. M.- Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine(2022) AIKAWA, Nadia E.; KUPA, Leonard V. K.; SILVA, Clovis A.; SAAD, Carla G. S.; PASOTO, Sandra G.; YUKI, Emily F. N.; FUSCO, Solange R. G.; SHINJO, Samuel K.; ANDRADE, Danieli C. O.; SAMPAIO-BARROS, Percival D.; PEREIRA, Rosa M. R.; CHASIN, Anna C. S.; SHIMABUCO, Andrea Y.; LUPPINO-ASSAD, Ana P.; LEON, Elaine P.; LOPES, Marta H.; ANTONANGELO, Leila; MEDEIROS-RIBEIRO, Ana C.; BONFA, EloisaObjectives. To assess immunogenicity of a heterologous fourth dose of an mRNA (BNT162b2) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac). Methods. A total of 164 ARD patients who were coronavirus disease 2019 (COVID-19) poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies-NAb) to the third dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) 3 months after last dose. IgG and NAb were evaluated before and after the fourth dose. Results. Significant increases were observed after the fourth dose in IgG (66.4 vs 95.1%, P < 0.001), NAb positivity (5.5 vs 83.5%, P < 0.001) and geometric mean titre (29.5 vs 215.8 AU/ml, P < 0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after a fourth dose were more frequently under rituximab (P = 0 .001) . Negative NAb was associated with older age (P = 0.015), RA (P = 0 .002) , SSc (P = 0 .026) , LEF (P = 0 .01 6) and rituximab use (P = 0.007) . In multiple logistic regression analysis, prednisone dose >= 7.5 mg/day (OR =0.34; P = 0.047) , LEF (OR =0.32, P = 0.036) and rituximab use (OR =0.19, P = 0.022) were independently associated with negative NAb after the fourth vaccine dose. Conclusions. This is the largest study to provide evidence of a remarkable humoral response after the fourth dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/non-response to the third dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose.
- Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control(2020) DINIS, Valquiria G.; VIANA, Vilma T.; LEON, Elaine P.; SILVA, Clovis A.; SAAD, Carla G.; MORAES, Julio C.; BONFA, Eloisa S.; MEDEIROS-RIBEIRO, Ana C.Objectives To evaluate long-term effects on gamma-globulins and autoantibodies of abatacept (ABA) versus tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients. Method Eighteen RA patients undergoing abatacept (ABA-RA) and 18 age/sex-matched patients treated with TNFi (TNFi-RA) were compared regarding clinical data, total gamma-globulins (TGG), specific subtypes (IgG, IgM, IgA), free light chains (FLC), IgM/IgG rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP3), and anti-mutated citrullinated vimentin (anti-MCV), assessed before and every 6 months, up to 24 months. Exclusion criteria: previous abatacept/rituximab or low TGG (< 0.7 g/dL). Results At baseline, female sex (78 vs. 78%), age (55 vs. 53 years), DAS28 (5.73 vs. 5.67), TGG (1.4 vs. 1.35 g/dL), IgG (1168 vs. 1079 mg/dL), IgM (107 vs. 113 mg/dL), IgA (333 vs. 322 mg/dL), kappa (342 vs. 249 mg/dL), lambda (170 vs. 150 mg/dL), IgM-RF (76 vs. 53 UI), IgG-RF (63 vs. 25 UI), anti-CCP3 (216 vs. 189 UI), and anti-MCV (202 vs. 102 UI) were comparable in ABA-RA and TNFi-RA (p > 0.05). Similar disease activity improvement was observed in both groups. In ABA-RA, significant decreases (p < 0.05) were observed in TGG (1.4 vs. 1.05 g/dL), IgG (1168 vs. 997), IgA (333 vs. 278 mg/dL), kappa (342 vs. 257 mg/dL), lambda (170 vs. 144 mg/dL), IgM-RF (76 vs. 37 UI), IgG-RF (65 vs. 24 UI), anti-CCP3 (216 vs. 183 UI), and anti-MCV (202 vs. 60 UI) at 6 months, without further decreases. In contrast, TNFi-RA showed no decrease in any of such parameters. ABA-RA also had more often transient IgG levels under the lower limit of normality (66.7% vs. 33.3%, p = 0.046). No severe infection occurred. DAS28, ESR, and CRP correlated significantly to gamma-globulins and FLC at baseline (p < 0.05), but these correlations were longitudinally lost in ABA-RA, but not in TNFi-RA. Conclusion ABA, but not TNFi, induces a safe, persistent, long-term, and non-progressive reduction in gamma-globulins and autoantibodies, including anti-MCV. This pattern is dissociated from disease activity control.
- 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.
- Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?(2012) BORBA, Eduardo F.; SAAD, Carla G. S.; PASOTO, Sandra G.; CALICH, Ana L. G.; AIKAWA, Nadia E.; RIBEIRO, Ana C. M.; MORAES, Julio C. B.; LEON, Elaine P.; COSTA, Luciana P.; GUEDES, Lissiane K. N.; SILVA, Clovis A. A.; GONCALVES, Celio R.; FULLER, Ricardo; OLIVEIRA, Suzimara A.; ISHIDA, Maria A.; PRECIOSO, Alexander R.; BONFA, EloisaObjective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) epsilon 20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED epsilon 20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED epsilon 20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED epsilon 20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED epsilon 20 mg + IS + CQ (57.4%; P = 0.09). Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity.
- Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switching(2020) BRUNELLI, Juliana Barbosa; SILVA, Clovis Almeida; PASOTO, Sandra Gofinet; SAA, Carla Goncalves Schahin; KOZU, Katia Tomie; GOLDENSTEIN-SCHAINBERG, Claudia; LEON, Elaine Pires; VENDRAMINI, Margarete B. G.; FONTOURA, Nicole; BONFA, Eloisa; AIKAWA, Nadia EmiObjective To assess the longitudinal production of anti-adalimumab antibody (AAA) and baseline risk factors for this antibody development in juvenile idiopathic arthritis (JIA) patients initiating adalimumab (ADA). Method Thirty consecutive JIA patients under ADA therapy were prospectively followed. JIA clinical/laboratorial/treatment data and sera for ADA and AAA assays (ELISA and bridging ELISA) were obtained at baseline (BL), 2 months (2M), 3 months (3M), 6 months (6M), 12 months (12M), and 24 months (24M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels). Results AAA was absent at BL, first detected at 2M after ADA initiation in 2/30 (7%) patients with a significant increase at 3M (10/29 (34%), p = 0.013) and no major change in 6M (11/30 (37%)) and 12M (9/26 (35%)). Of note, at 3M, AAA levels correlated negatively with ADA levels (r = - 0.781, p = 0.0001). Analysis of BL predictors revealed a significantly higher risk of developing AAA in patients with female gender (OR 21; 95% CI 1.08-406.57; p = 0.044), ESR > 30 mm/1st hour (OR 5.44; 95% CI 1.04-28.53; p = 0.045), and leflunomide use (OR 9.33; 95% CI 1.51-57.66; p = 0.016). In contrast, concomitant use of methotrexate was protective for AAA appearance (OR 0.08; 95% CI 0.01-0.53; p = 0.009). After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared with 15% in AAA-negative group (p = 0.03). Conclusions This study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 24M. We also identified female gender, increased ESR, and leflunomide use as relevant risk factors for AAA production at BL, whereas methotrexate was protective. Early systematic monitoring of AAA at 3M may, therefore, guide drug switching in these patients.
conferenceObject Anti-Adalimumab Antibodies Kinetics: An Early Guide for Juvenile Idiopathic Arthritis (JIA) Switching(2018) BRUNELLI, Juliana; SILVA, Clovis A.; PASOTO, Sandra G.; SAAD, Carla G. S.; KOZU, Katia T.; LEON, Elaine P.; VENDRAMINI, Margarete B.; FONTOURA, Nicole; BONFA, Eloisa; AIKAWA, Nadia E.