MICHELLE REMIAO UGOLINI LOPES
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 CORRELATION BETWEEN SHORTER DISEASE DURATION IN SYSTEMIC SCLEROSIS (SSC) AND ANTI-COLLAGEN TYPE V(2014) UGOLINI, M.; MANTOVANI, E.; DINIS, V.; BONOLDI, V.; RIBEIRO, A.; YOSHINARI, N.; ANDRADE, D.- 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.
- Antiphospholipid syndrome damage index (DIAPS): distinct long-term kinetic in primary antiphospholipid syndrome and antiphospholipid syndrome related to systemic lupus erythematosus(2020) TORRICELLI, A. Kuhl; UGOLINI-LOPES, M. Remiao; BONFA, E.; ANDRADE, D.Background Antiphospholipid syndrome (APS) is an acquired thrombophilia that affects young productive individuals, with permanent damage and negative impact on quality of life. Recently, a damage index specific for APS (DIAPS) was developed. There are, however, no data regarding the comparison of its performance and long-term damage in primary antiphospholipid syndrome (PAPS) and APS related to systemic lupus erythematosus (SLE; APS + SLE). The primary purpose of this study was therefore to compare the long-term damage in patients with these conditions. Methods This is a retrospective analysis of a single tertiary center cohort followed for approximately 10 years using a standardized prospective electronic chart database. Fifty consecutive PAPS patients age matched with 50 APS+SLE patients were consecutively selected for the study, and DIAPS was calculated once a year during follow-up. Long-term damage and damage kinetics in both groups were compared. Results PAPS and APS + SLE had comparable age (47.10 +/- 12.4 vs. 44.04 +/- 10.80 years; p = 0.19) and time of follow-up (9.40 +/- 3.60 vs. 10.94 +/- 4.50 years; p = 0.06). At diagnosis, PAPS had higher DIAPS than APS + SLE (1.72 +/- 1.17 vs. 0.82 +/- 0.96; p < 0.001). At the end of the 10-year follow-up, both groups presented comparable mean damage scores (2.04 +/- 1.50 vs. 2.24 +/- 1.61; p = 0.52). The damage increment throughout the observation period for PAPS was solely 35%, whereas for APS + SLE it was gradual, persistent and reached 139% at the end of follow-up, with a total damage increment for PAPS lower than APS + SLE (0.43 +/- 0.30 vs. 1.22 +/- 1.24; p < 0.001). Of note, the frequency of individuals who acquired damage was lower in PAPS than in APS + SLE (32% vs. 71%; p < 0.001). PAPS also had a longer delay in diagnosis than APS + SLE (4.00 +/- 4.20 vs. 2.54 +/- 3.05 years; p = 0.04). This delay was positively correlated with a higher damage score at diagnosis (r = 0.36, p < 0.001) in all groups. Conclusion We identified a distinct pattern of damage in PAPS and APS related to SLE. Damage in PAPS is an early event, while APS+SLE is associated with higher long-term damage, with a striking increment of damage along the follow-up. A diagnosis delay is correlated with higher damage scores. Damage surveillance therefore requires different approaches for these two conditions.
- Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases(2022) AIKAWA, Nadia Emi; KUPA, Leonard de Vinci Kanda; MEDEIROS-RIBEIRO, Ana Cristina; SAAD, Carla Goncalves Schahin; YUKI, Emily Figueiredo Neves; PASOTO, Sandra Gofinet; ROJO, Priscila Tagliaferro; PEREIRA, Rosa Maria Rodrigues; SHINJO, Samuel Katsuyuki; SAMPAIO-BARROS, Percival Degrava; ANDRADE, Danieli Castro Oliveira; HALPERN, Ari Stiel Radu; FULLER, Ricardo; SOUZA, Fernando Henrique Carlos; GUEDES, Lissiane Karine Noronha; ASSAD, Ana Paula Luppino; MORAES, Julio Cesar Bertacini de; LOPES, Michelle Remiao Ugolini; MARTINS, Victor Adriano de Oliveira; BETANCOURT, Lorena; RIBEIRO, Carolina Torres; SALES, Lucas Peixoto; BERTOGLIO, Isabela Maria; BONOLDI, Virginia Lucia Nazario; MELLO, Renata Lys Pinheiro; BALBI, Gustavo Guimaraes Moreira; SARTORI, Ana Marli Christovam; ANTONANGELO, Leila; SILVA, Clovis Artur; BONFA, EloisaObjective To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response. Methods Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination. Results ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone >= 5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone >= 5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001). Conclusions We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX.
- Anti-collagen type v: a marker of early systemic sclerosis?(2019) UGOLINI-LOPES, Michelle R.; MANTOVANI, Elenice; BONOLDI, Virginia Lucia N.; RIBEIRO, Ana Cristina de Medeiros; BONFA, Eloisa; YOSHINARI, Natalino; ANDRADE, DanieliObjective: To evaluate the frequency of anti-collagen type V in humans with early systemic sclerosis (SSc) compared to defined SSc patients and healthy controls, since collagen type V was shown to be overexpressed in early SSc patients' skin and there is no data concerning the presence of this antibody in early stages of human SSc. Experimental studies showed that animal models immunized with collagen type V developed a disease similar to human systemic sclerosis (SSc), with antibodies production, mainly in early stages post-immunization. Methods: Eighty-one female SSc patients were included and divided into two groups: early-SSc (18 patients-EULAR Preliminary Criteria) and defined-SSc (63 patients-ACR Criteria 1980). The control group consisted of 19 healthy women age-matched to Early-SSc group. Anti-collagen type V was performed by ELISA. Data was analyzed by appropriate tests. Results: The prevalence of anti-collagen type V in early-SSc, defined-SSc and control groups was respectively 33, 17 and 5% (p = 0.07). SSc patients with anti-collagen type V had shorter disease duration compared to those without this antibody (8.8 +/- 5.1 vs. 14.7 +/- 8.9, p = 0.006). Likewise, early-SSc patients with anti-collagen V also had a shorter disease duration than patients negative for this antibody (4.6 +/- 2.2 vs. 9.7 +/- 5.2, p = 0.04). No association with clinical subsets or scleroderma antibodies specificities was observed (p > 0.05). Conclusion: The production of anti-collagen type V in SSc seems to be an early event independent of other antibodies specificities. Further studies are necessary to determine if the underlying mechanism for this chronology involves a primary immune response to abnormal expression of collagen type V.
- Enhanced type I interferon gene signature in primary antiphospholipid syndrome: Association with earlier disease onset and preeclampsia(2019) UGOLINI-LOPES, Michelle Remiao; TORREZAN, Giovana Tardin; GANDARA, Ana Paula Rossi; OLIVIERI, Eloisa Helena Ribeiro; NASCIMENTO, Iana Souza; OKAZAKI, Erica; BONFA, Eloisa; CARRARO, Dirce Maria; ANDRADE, Danieli Castro Oliveira deObjective: Recently, two studies demonstrated that a relevant percentage of primary antiphospholipid syndrome (PAPS) patients had an upregulation of interferon (IFN) genes. However, 20%-28% of these patients had anti-dsDNA, a highly specific systemic lupus erythematosus (SLE) autoantibody. This study aimed to determine the prevalence of the type I IFN signature in the peripheral blood mononuclear cells of PAPS patients without specific SLE autoantibodies and search for its clinical associations. Methods: Fifty-three PAPS patients (Sydney's criteria) were consecutively selected and age-matched with 50 healthy controls. A third group of nonimmune-mediated thrombophilia patients was also included. The expression of 41 IFN-induced genes was analyzed using real time quantitative PCR. A principal component analysis determined which genes composed the IFN signature, and the z-score was calculated. An ROC curve defined the signature cut-off. Results: Six genes remained in the IFN signature DNAJA1, IFIT5, IF127, MX1, IF16, and TYK2. The ROC cutoff was 3.9-fold (AUC = 0.706, S = 0.49, E = 0.86, PPV = 0.79, NPV = 0.61). The type I IFN signature was present in 49% of the patients with PAPS compared with 14.0% of the healthy controls and 17% of the nonimmunemediated thrombophilia patients (p < .0001). The IFN signature was associated with a younger age at the first antiphospholipid syndrome event (p = .023) and with preeclampsia (p = .032). Conclusion: Our results indicate that PAPS patients without lupus-specific antibodies have an enhanced type IFN gene signature that is not observed in nonimmune-mediated thrombophilia. Also, this overexpression of type I IFN-regulated genes associated with an earlier onset of antiphospholipid syndrome event and preeclampsia.
conferenceObject Antiphospholipid Syndrome Alliance for Clinical Trials & International Networking (APS ACTION) Clinical Database and Repository (""Registry"") Analysis: First and Recurrent Thrombosis Risk after 1201 Patient-Years of Follow-up(2017) UNLU, Ozan; ANDRADE, Danieli; BANZATO, Alessandra; BRANCH, D. Ware; FORTIN, Paul R.; GEROSA, Maria; LEVY, Roger A.; LOPES, Michelle; PETRI, Michelle; RODRIGUEZ, Ignasi; TEKTONIDOU, Maria; UGARTE, Amaia; WILLIS, Rohan; ERKAN, Doruk- Update on antiphospholipid antibody syndrome(2017) LOPES, Michelle Remião Ugolini; DANOWSKI, Adriana; FUNKE, Andreas; RêGO, Jozelia; LEVY, Roger; ANDRADE, Danieli Castro Oliveira deSummary Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations) add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE) but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy.
bookPart Síndrome antifosfolípide(2021) LOPES, Michelle Remião Ugolini; ANDRADE, Danieli Castro Oliveira deconferenceObject Cognitive dysfunction (CD) and serum levels of brain-derived neurotrophic factor (BDNF) in primary antiphospholipid syndrome(2019) ROSA, Renata; UGOLINI-LOPES, Michelle Remiao; GANDARA, Ana Paula Rossi; CAMPANHOLO, Kenia Repiso; DUTRA, Livia; ANDRADE, Danieli Castro Oliveira de