NADIA EMI AIKAWA
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).
- Risk factors for mortality in 1528 Brazilian childhood-onset systemic lupus erythematosus patients(2023) SAKAMOTO, Ana P.; SILVA, Clovis A.; PITA, Ana C.; TRINDADE, Vitor C.; ISLABAO, Aline G.; FIOROT, Fernanda J.; LOPES, Sandra R. M.; PEREIRA, Rosa M. R.; SAAD-MAGALHAES, Claudia; RUSSO, Gleice C. S.; LEN, Claudio A.; PRADO, Rogerio do; CAMPOS, Lucia M. A.; AIKAWA, Nadia E.; APPENZELLER, Simone; FERRIANI, Virginia P. L.; SILVA, Marco F.; FELIX, Marta; FONSECA, Adriana R.; ASSAD, Ana P. L.; SZTAJNBOK, Flavio R.; SANTOS, Maria C.; BICA, Blanca E.; SENA, Evaldo G.; MORAES, Ana J.; FRAGA, Melissa M.; ROBAZZI, Teresa C.; SPELLING, Paulo F.; SCHEIBEL, Iloite M.; CAVALCANTI, Andre S.; MATOS, Erica N.; GUIMARAES, Luciano J.; SANTOS, Flavia P.; MOTA, Licia M. H.; BONFA, Eloisa; TERRERI, Maria T.Objectives: To identify associations between mortality in cSLE patients and their characteristics: clinical and laboratory features, disease activity and damage scores, and treatment; to evaluate risk factors associated with mortality in cSLE; and to determine the most frequent causes of death in this group of patients.Methods: We performed a multicenter retrospective cohort using data from 1,528 cSLE patients followed in 27 pediatric rheumatology tertiary centers in Brazil. Patients' medical records were reviewed according to a standardized protocol, in which information regarding demographic and clinical features, disease activity and damage scores, and treatment were collected and compared between deceased cSLE patients and survivors. Univariate and multivariate analyses by Cox regression model were used to calculate risk factors for mortality, whereas survival rates were analyzed by Kaplan-Meier plots.Results: A total of 63/1,528 (4.1%) patients deceased, 53/63 were female (84.1%), median age at death was 11.9 (9.4-13.1) years and median time interval between cSLE diagnosis and death was 3.2 (0.5-5.3) years. Sepsis was the main cause of death in 27/63 (42.8%) patients, followed by opportunistic infections in 7/63 (11.1%), and alveolar hemorrhage in 6/63 (9.5%) patients. The regression models resulted in neuropsychiatric lupus (NP-SLE) (HR = 2.56, 95% CI = 1.48-4.42) and chronic kidney disease (CKD) (HR = 4.33, 95% CI = 2.33-4.72), as risk factors significantly associated with mortality. Overall patient survival after cSLE diagnosis at 5, 10, and 15 years were 97%, 95.4%, and 93.8%, respectively.Conclusions: This study confirmed that the recent mortality rate in cSLE in Brazil is low, but still of concern. NP-SLE and CKD were the main risk factors for mortality, indicating that the magnitude of these manifestations was significantly high.
conferenceObject NUTRITIONAL ASSESSMENT, BODY COMPOSITION AND PHASE ANGLE IN JUVENILE DERMATOMYOSITIS PATIENTS(2023) PUGLIESE, Camila; KOZU, Katia T.; CAMPOS, Lucia M. A.; AIKAWA, Nadia E.; SILVA, Clovis A. A.; ELIAS, Adriana M.- Bone erosions associated with systemic bone loss on HR-pQCT in women with longstanding polyarticular juvenile idiopathic arthritis(2023) RIBEIRO, Surian Clarisse C. R.; SALES, Lucas P.; FERNANDES, Alan L.; PEREZ, Mariana O.; TAKAYAMA, Liliam; CAPARBO, Valeria F.; ASSAD, Ana Paula L.; AIWAKA, Nadia E.; GOLDENSTEIN-SCHAINBERG, Claudia; BORBA, Eduardo F.; DOMICIANO, Diogo S.; FIGUEIREDO, Camille P.; PEREIRA, Rosa M. R.Objectives: To analyze longstanding polyarticular juvenile idiopathic arthritis (pJIA) for possible associations between localized bone damage (erosions), and systemic bone loss. Besides, to compare the systemic bone mass of pJIA with healthy controls. Methods: Thirty-four pJIA women and 99 healthy controls (HC) were included. Radius and tibia of all subjects were scanned by HR-pQCT. Volumetric bone mineral density (vBMD), bone microarchitecture, and -finite element parameters were analyzed. Patients underwent HR-pQCT of 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the dominant hand, for bone erosions quantification. Results: The mean age of patients was 31.5 +/- 7.4yrs with a mean disease duration of 21.7 +/- 9.2yrs. Bone erosions were detectable in 79% of patients. The number of bone erosions was positively correlated with cortical porosity (Ct.Po) at tibia (r = 0.575, p = 0.001), and radius (r = 0.423, p = 0.018); and negatively correlated with cortical vBMD at tibia (r=-0.420, p = 0.015). In a logistic regression analysis, adjusted for anti-CCP, the presence of bone erosions was independently associated with Ct.Po at radius (p = 0.018) and cortical vBMD at tibia (p = 0.020). Moreover, cortical and trabecular vBMD, trabecular number, and mu-finite element parameters were decreased in patients compared to HC (p < 0.05). Conclusion: Bone erosions in longstanding pJIA women were associated with decreased cortical bone parameters, and these patients showed systemic bone impairment at peripheral sites compared with healthy controls.
- Body Composition and Phase Angle: How to Improve Nutritional Evaluation in Juvenile Dermatomyositis Patients(2023) PUGLIESE, Camila; DELGADO, Artur Figueiredo; KOZU, Katia Tomie; CAMPOS, Lucia Maria de Arruda; AIKAWA, Nadia Emi; SILVA, Clovis Artur; ELIAS, Adriana Maluf(1) Background: This study aimed to assess body composition (BC) using bioelectrical impedance and food intake in juvenile dermatomyositis (JDM) patients. Associations between BC and physical activity, disease activity/cumulative damage and health-related quality of life parameters were also evaluated; (2) Methods: This was a cross-sectional study with 30 consecutive JDM patients (18 female and 12 male) and 24 healthy volunteers (14 female and 10 male) of both sexes followed at our pediatric rheumatology unit. The gathering of anthropometric and dietary data, and the performance of physical activity and bioelectrical impedance were undertaken in face-to-face meetings and through questionnaires. Clinical and therapeutic data were collected from medical records according to information from routine medical appointments; (3) Results: The frequency of high/very high body fat was significantly higher in controls compared with JDM patients (66.7% vs. 91.7%; p = 0.046). The median phase angle was significantly lower in patients compared with controls (5.2 & PLUSMN; 1.3 vs. 6.1 & PLUSMN; 1.0; p = 0.016). Body fat and lean mass were positively correlated with disease duration (r(s) = +0.629, p < 0.001 and r(s) = +0.716, p < 0.001, respectively) and phase angle (PhA) (r(s) = +0.400, p = 0.029 and r(s) = +0.619, p < 0.001, respectively). JDM patients with PhA & GE; 5.5 presented higher lean mass when compared with patients with PhA < 5.5 (p = 0.001); (4) Conclusions: Bioelectrical impedance can be a useful auxiliary exam in the medical and nutritional follow-up of JDM patients, because it seems to impact functional ability. These findings may assist professionals when advising JDM patients about the importance of physical activity and healthy eating in the preservation of lean mass.
- Short-term Accrual 2019 European League Against Rheumatism/American College of Rheumatology Domains and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage in Lupus Patients With and Without Nephritis at Disease Onset(2023) MUNHOZ, Gabriela A.; AIKAWA, Nadia E.; SILVA, Clovis A.; PASOTO, Sandra G.; PEDROSA, Tatiana N.; SEGURO, Luciana P. C.; BONFA, Eloisa; BORBA, Eduardo F.ObjectiveTo determine in a historical inception cohort the impact of lupus nephritis at disease onset in short-term accrual 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) domains. The possible association with treatment and damage was also investigated.MethodsOne hundred thirty-three consecutive adult systemic lupus erythematosus patients according to the 2019 EULAR/ACR criteria were divided according to the presence (RENAL-lupus) or absence of renal involvement (NONRENAL-lupus) at disease onset. The 2019 EULAR/ACR score and Systemic Lupus International Collaborating Clinics/ACR (SDI) were longitudinally evaluated over 3 years.ResultsRENAL-lupus (n = 49 [36.8%]) and NONRENAL-lupus (n = 84 [63.2%]) were similar regarding age (p = 0.704), female sex (p = 0.313), and black race (p = 0.506). At study entry, RENAL-lupus had higher 2019 EULAR/ACR total domains (30 [12-42] vs. 22 [10-36], p < 0.001) and used more often glucocorticoid (p < 0.001), mycophenolate mofetil (p = 0.007), and cyclophosphamide (p = 0.001). After 3 years, a stable number of domain scores was observed for the RENAL-lupus (30 [12-42] vs. 30 [12-42], p = 0.125), whereas an increase was observed for the NONRENAL-lupus (22 [10-36] vs. 23 [10-40], p < 0.001) compared with baseline. Accordingly, RENAL-lupus patients had a lower frequency of additional domains (3/49 [6.1%] vs. 37/84 [44.0%], p < 0.0001). New kidney involvement occurred in 15 (44.1%) of 34 patients of the NONRENAL-lupus. Both groups evolved with a comparable increase in frequency of patients with damage (SDI >= 1) at the end of the study (23/49 [46.9%] vs. 34/89 [40.54%], p = 0.585) with a similar median of SDI (1 [0-4] vs. 0 [0-2], p = 0.132).ConclusionsThe distinct pattern of accrual 2019 EULAR/ACR domains in patients with and without nephritis at disease onset suggests that close surveillance for additional organ involvement, including kidney, is mandatory in NONRENAL lupus in the first 3 years of disease. The unexpected comparable early damage in both groups despite milder disease and less intense immunosuppression in NONRENAL lupus reinforces the need for new and tailored therapies for these patients.
- 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.
- No Associations Between Physical Activity and Immunogenicity in SARS-CoV-2 Seropositive Patients With Autoimmune Rheumatic Diseases Prior to and After Vaccination(2023) SMAIRA, Fabiana Infante; MAZZOLANI, Bruna Caruso; LEMES, italo Ribeiro; SILVA, Rafael Pires da; PINTO, Ana J.; SIECZKOWSKA, Sofia M.; AIKAWA, Nadia E.; PASOTO, Sandra G.; MEDEIROS-RIBEIRO, Ana C.; SAAD, Carla G. S.; YUK, Emily F. N.; SILVA, Clovis A.; SWINTON, Paul; KUPA, Leonard de Vinci Kanda; HALLAL, Pedro C.; ROSCHEL, Hamilton; GUALANO, Bruno; BONFA, EloisaAim: To investigate the association between physical activity and immunogenicity among SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases prior to and following a 2-dose schedule of CoronaVac (Sinovac inactivated vaccine). Methods: This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial conducted in Sao Paulo, Brazil. In this substudy, only SARS-CoV-2 seropositive patients were included. Immunogenicity was assessed by seroconversion rates of total anti-SARS-CoV-2 S1/S2 immunoglobulin G (IgG), geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity before and after vaccination. Physical activity was assessed through a questionnaire. Model-based analyses were performed controlling for age (<60 or>_60 y), sex, body mass index (<25, 25-30, and >30 kg/m2), and use of prednisone, immunosuppressants, and biologics. Results: A total of 180 seropositive autoimmune rheumatic disease patients were included. There was no association between physical activity and immunogenicity before and after vaccination. Conclusions: This study suggests that the positive association between physical activity and greater antibody responses seen in immunocompromised individuals following vaccination is overridden by previous SARS-CoV-2 infection, and does not extend to natural immunity.
- Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose(2023) PEREIRA, Rosa M. R.; DAGOSTIN, Marilia A.; CAPARBO, Valeria F.; SALES, Lucas P.; PASOTO, Sandra G.; SILVA, Clovis A.; YUKI, Emily F. N.; SAAD, Carla G. S.; MEDEIROS-RIBEIRO, Ana C.; KUPA, Leonard V. K.; FUSCO, Solange R. G.; MARTINS, Victor A. O.; MARTINS, Carolina C. M. F.; BARBAS, Carmen Valente; SHINJO, Samuel K.; AIKAWA, Nadia E.; BONFA, EloisaObjective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients.Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vac-cine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Anti-bodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240).Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- posi-tivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naive-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and predni-sone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with pred-nisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05-0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05-0.88, p = 0.034). After six months (D69 -D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduc-tion occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attribut-able to the vaccine were observed.Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).
- Primary dental care treatment in primary Sjogren's syndrome: a possible role in improving salivary flow rate(2022) MARTINS, V. A. O.; FLORIANO, T. F.; LEON, E. P.; VILLAMARIN, L. E. B.; DEVEZA, G. B. H.; AIKAWA, N. E.; SILVA, C. A. A.; KUPA, L. V. K.; PERES, M. P. S. M.; BRAZ-SILVA, P. H.; BONFA, E.; PASOTO, S. G.Objective Primary Sjogren's syndrome (pSS) is an inflammatory chronic disorder that mainly affects exocrine glands. Additionally, oral infections can aggravate the glandular dysfunction. However, data on primary dental care (PDC) treatment in pSS are scarce. This study aimed to appraise the impact of PDC on the Xerostomia Inventory (XI), unstimulated/stimulated salivary flow rates and salivary cytokine profile in pSS. Methods Fifty-two pSS patients and 52 sex- and age-matched control participants without systemic autoimmune diseases were included in a prospective study. At inclusion, all participants were assessed through a standardised protocol, measurement of salivary pro-inflammatory cytokines, and underwent PDC. Dental procedures included: oral hygiene guidance, restorative treatment of caries, surgical removal of residual roots and impacted or partially erupted teeth, cysts, supra and subgingival periodontal scaling and treatment of soft tissue disorders (removal of lesions and treatment of opportunistic infections). After 3 months, the clinical/laboratorial assessments were repeated. Results At inclusion, the Decayed, Missing and Filled Teeth (DMFT) index was higher in the pSS patients than in the control group (13.3 +/- 8.2 vs. 8.6 +/- 6.2, p=0.002), whereas periodontal parameters were comparable in both groups (p>0.05). After PDC, 26.9% of pSS patients showed a reduction of at least 6 points (clinical improvement) in XI, but mean XI remained unchanged (p=0.285). PDC resulted in an increase in mean unstimulated (p<0.001) and stimulated (p=0.001) salivary flow rates in pSS, with no change in salivary cytokine profile (p=0.05). Conclusion PDC promoted improvement in unstimulated and stimulated salivary flow rates in pSS. This novel finding reinforces the recommendation of this strategy for pSS patients. Clinicaltrials.gov (Identifier: NCT03711214).