VILMA DOS SANTOS TRINDADE VIANA
Projetos de Pesquisa
Unidades Organizacionais
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Dyslipidemia in Juvenile Dermatomyositis: The Role of Disease Activity(2012) KOZU, Katia T.; SILVA, Clovis Artur; BONFA, Eloisa; SALLUM, Adriana M.; PEREIRA, Rosa M. R.; VIANA, Vilma S.; BORBA, Eduardo F.; CAMPOS, Lucia M. A.article 22 Citação(ões) na Scopus Dyslipidaemia in juvenile dermatomyositis: the role of disease activity(2013) KOZU, K. T.; SILVA, C. A.; BONFA, E.; SALLUM, A. M.; PEREIRA, R. M. R.; VIANA, V. S.; BORBA, E.; CAMPOS, L. M.Objective To evaluate the presence of dyslipidaemia in JDM and its possible risk factors. Methods Twenty-five JDM patients were compared to 25 healthy controls according to demographic data, body composition, fasting lipoproteins, glycaemia, insulin, antibodies and muscle enzymes. JDM scores were assessed: CMAS, MMT, DAS, MYOACT and MYTAX. Results Abnormal lipid profile was found in nine patients and four controls (36% vs. 16%, p=0.196). TDM patients demonstrated significant higher levels of triglycerides (TG) [80(31-340) vs. 61(19-182) mgldL, p=0.011 j and higher frequency of abnormal levels of high density lipoproteins (HDL) (28% vs. 4%, p=0.04) when compared to controls. JDM patients with dyslipidaemia demonstrated significant lower median of HDL levels 129(0-49) vs. 50(39-72) mgldL, p=0.0005, higher frequency of low HDL levels (77% vs. 0%, p=0.0001),.higher TG levels [128(31-340) vs. 69(46-138) mgldL, p=0.011), and also a higher frequency of increased levels of TG (44% vs. 0%, p=0.01), and TC (33% vs. 0%, p=0.03) when compared to those without this condition. Positive anti-LPL antibody was detected in just one JDM patient with abnormal lipid profile. JDM with dyslipidaemia had higher ESR (26 vs. I 4.5mmllsthour, p=0.006), CRP (2.1 vs. 0.4mgldL, p=0.01), DAS (6 vs. 2, p=0.008), MYOACT(0.13 vs. 0.01, p=0.012), MYTAX(0.06vs.0,p=0.018), and lower scores of CMAS (47 vs. 52, p=0.024) and MMT (78 vs. 80, p=0.001) compared to JDM without dyslipidaemia. Positive correlations were detected between TG levels and CRP (7-.19.697, p=0.001), DAS (r-0.610, p=0.001), MYOACT (r=0.661, p=0.001),114YTAX (r-0.511, p=0.008), and negative correlations with CMAS (r=-0.506, p=0.009) and MMT (r=-0.535, p=0.005). No differences were found between these groups regarding body composition, lipodystrophy, anti-LPL antibodies, and treatment except by higher frequency of cyclosporine current use in patients with dys.lipidaemia (33% vs. 0%, p=0.03). Conclusions Dyslipidaemia in JDM patients was characterised by increased levels of TG and low levels of HDL. Disease activity and cyclosporine use were the mainly factors associated to these abnormalities.- Anti-DNase I Antibody A New Serological Reactivity in Primary Sjogren Syndrome(2020) GRIFFO, Priscilla; VIANA, Vilma V. S. T.; PASOTO, Sandra G.; LEON, Elaine P.; BONFA, EloisaBackground and Objective: Primary Sjogren syndrome (pSS) is a systemic autoimmune rheumatic disease that particularly affects exocrine glands. Dry eye is one of the most important features of this syndrome, and a recent study reported reduced deoxyribonuclease I (DNase I) activity in the tear of patients with dry eye. We therefore postulated that patients with pSS might have antibodies targeting DNAse I. Methods: We have evaluated in a cross-sectional study 85 patients with pSS (2002 American-European Consensus Group Criteria), 50 rheumatoid arthritis (RA) patients (1987 American College of Rheumatology Criteria) without sicca symptoms, and 88 healthy volunteers. IgG anti-DNase I was detected by enzyme-linked immunosorbent assay using as antigen bovine pancreas enzyme and confirmed by immunoblotting. Results: Age and sex were alike in the 3 groups (p > 0.05). Anti-DNase I was detected in 43.5% of the pSS patients. In contrast, this reactivity was absent in all RA patients (p = 0.0001). Additional comparison of pSS patients with (n = 37) or without (n = 48) anti-DNase I showed that the former group had higher IgG serum levels (2293.2 +/- 666.2 vs 1483.9 +/- 384.6 mg/dL, p = 0.0001) and greater rate of non-drug-induced leukopenia (43% vs 19%, p = 0.02). A multivariate logistic regression analysis identified that only IgG levels were independently associated with anti-DNase I. Conclusions: We describe a high frequency of anti-DNase I antibodies in pSS patients associated with higher serum IgG levels. The lack of this reactivity in RA patients without sicca symptoms suggests that this antibody may be helpful in the differential diagnosis of these diseases.
- Ribosomal P antibody: 30 years on the road(2017) VIANA, V. T.; DURCAN, L.; BONFA, E.; ELKON, K. B.The identity of the protein antigens targeted by anti-cytoplasmic antibodies in lupus was discovered 30 years ago. These antigens are three acidic ribosomal phosphoproteins, P0, P1, and P2. Precise identification of the shared epitope on these three proteins enabled sensitive and specific immunoassays to be developed. Anti-P antibodies are highly specific for systemic lupus erythematosus (SLE) and occur in 15%-35% of patients, depending on ethnicity as well as the age of onset. Increased frequencies of detection of anti-P have been reported in childhood SLE as well as in neuropsychiatric, renal, and hepatic disease. While longitudinal studies by the Systemic Lupus International Collaborating Clinics (SLICC) consortium supported the association of anti-P with neuropsychiatric lupus, the predictive value of antibody determination remains controversial. This is likely explained by the heterogeneity of neuropsychiatric lupus as well as by the different methodologies used for assay. A number of experimental studies have suggested a direct pathogenic role for anti-P antibodies in brain disease. Findings include cross reactivity between anti-P and a neuronal surface antigen, which was detected in areas of the brain involved in memory, cognition, and emotion. Direct injection of anti-P antibodies into the brains of rodents was also associated with abnormal electrical activity and behavioral disturbances. Taken together, research over the last 30 years has established anti-P antibodies as a useful diagnostic marker of SLE and at least a subset of patients with neuropsychiatric disease. Further research is required to fine tune the association of anti-P with clinical manifestations and establish beyond high probability a pathophysiologic role for the antibodies.
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.- Ovarian reserve in adult patients with childhood-onset lupus: a possible deleterious effect of methotrexate?(2014) ARAUJO, D. B. de; YAMAKAMI, L. Y. S.; AIKAWA, N. E.; BONFA, E.; VIANA, V. S. T.; PASOTO, S. G.; PEREIRA, R. M. R.; SERAFIN, P. C.; BORBA, E. F.; SILVA, C. A.Objectives: To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE). Method: Fifty-seven adult c-SLE female patients and 21 healthy controls were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Mullerian hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual abnormalities, disease activity, damage, and treatment were also analysed. Results: The median current age was similar in adult c-SLE patients and controls (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p = 0.037) and AFC (6 vs. 16, p < 0.001) were significantly reduced in SLE patients compared to controls without significant menstrual abnormalities. Anti-CoL were solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated with demographic data, ovarian reserve parameters, disease activity/damage, and treatment. Further evaluation of c-SLE patients treated with cyclophosphamide revealed a higher median of FSH levels compared to c-SLE patients not treated with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs. 16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with methotrexate demonstrated a negative correlation between the cumulative dose and AMH levels (p = 0.027, r = -0.507). Conclusions: The present study demonstrated for the first time that a high cumulative methotrexate dose is a possible cause of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are required to confirm this deleterious effect in other rheumatic diseases, particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.
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.- Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases(2011) SAAD, Carla G. S.; BORBA, Eduardo F.; AIKAWA, Nadia E.; SILVA, Clovis A.; PEREIRA, Rosa M. R.; CALICH, Ana Luisa; MORAES, Julio C. B.; RIBEIRO, Ana C. M.; VIANA, Vilma S. T.; PASOTO, Sandra G.; CARVALHO, Jozelio F.; FRANCA, Ivan L. A.; GUEDES, Lissiane K. N.; SHINJO, Samuel K.; SAMPAIO-BARROS, Percival D.; CALEIRO, Maria T.; GONCALVES, Celio R.; FULLER, Ricardo; LEVY-NETO, Mauricio; TIMENETSKY, Maria do Carmo S.; PRECIOSO, Alexander R.; BONFA, EloisaBackground Despite the WHO recommendation that the 2010-2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behcet's disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjogren's syndrome, Takayasu's arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener's) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p < 0.0001), seroconversion rates (63.4% vs 76.9%, p < 0.001) and the factor increase in GMT (8.9 vs 13.2 p < 0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p < 0.0001), RA (p < 0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p < 0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)
- Reduced ovarian reserve in patients with adult polymyositis(2015) SOUZA, Fernando Henrique Carlos de; SILVA, Clovis Artur da; YAMAKAMI, Lucas Yugo Shiguehara; VIANA, Vilma dos Santos Trindade; BONFA, Eloisa; SHINJO, Samuel KatsuyukiPolymyositis (PM) affects female gender during reproductive age; however, there is no study assessing ovarian reserve in these patients to evaluate ovarian reserve markers in PM. Eight female patients with PM (Bohan and Peter criteria, 1975) with aged 18-40 years, followed at our tertiary centre from March 2011 to May 2014, were invited to participate. They were age-matched with 16 healthy individuals (control group). All were evaluated at early follicular phase of menstrual cycle. Follicle stimulating hormone (FSH), estradiol, inhibin B, anti-Mullerian hormone (AMH) serum levels (ELISA) and sonographic antral follicle count (AFC) were determined. PM patients and controls had comparable mean age (31.4 +/- 6.5 vs. 30.7 +/- 6.2 years, P = 0.946), ethnicity and socioeconomic class (P > 0.05). PM mean age of onset was 27.3 +/- 6.5 years and disease duration of 6.5 +/- 4.1 years. Menstrual cycles were alike in both groups with a similar frequency of age at menarche, gynaecological age, duration and length of menstrual cycle (P > 0.05). The median serum level of AMH was significantly lower in PM compared to controls [0.7(0.3-3.4) vs. 3.1(1.4-4.0), P = 0.021]. AMH levels a parts per thousand currency sign1 ng/mL (50 vs. 6.3 %, P = 0.024) and very low AFC (37.5 vs. 6.3 %, P = 0.037) were significantly in PM patients versus controls. The other hormones (FSH, inhibin B and estradiol levels) were similar between both groups (P > 0.05). The present study was the first to identify subclinical ovarian dysfunction in PM patients during reproductive ages. Further study is necessary to assess the possible role of PM-related factors that may influence the ovarian function of these patients.
- Myositis-specific and myositis-associated autoantibody profiles and their clinical associations in a large series of patients with polymyositis and dermatomyositis(2013) CRUELLAS, Marcela Gran Pina; VIANA, Vilma dos Santos Trindade; LEVY-NETO, Mauricio; SOUZA, Fernando Henrique Carlos de; SHINJO, Samuel KatsuyukiOBJECTIVE: To analyze the prevalence of myositis-specific and myositis-associated autoantibodies and their clinical correlations in a large series of patients with dermatomyositis/polymyositis. METHOD: This cross-sectional study enrolled 127 dermatomyositis cases and 95 polymyositis cases. The disease-related autoantibody profiles were determined using a commercially available blood testing kit. RESULTS: The prevalence of myositis-specific autoantibodies in all 222 patients was 34.4%, whereas myositis-associated autoantibodies were found in 41.4% of the patients. The most frequently found autoantibody was anti-Ro-52 (36.9%), followed by anti-Jo-1 (18.9%), anti-Mi-2 (8.1%), anti-Ku (4.1%), anti-SRP (3.2%), anti-PL-7 (3.2%), anti-PL-12 (2.7%), anti-PM/Scl75 (2.7%), and anti-PM/Scl100 (2.7%). The distributions of these autoantibodies were comparable between polymyositis and dermatomyositis, except for a higher prevalence of anti-Jo-1 in polymyositis. Anti-Mi-2 was more prevalent in dermatomyositis. Notably, in the multivariate analysis, anti-Mi-2 and anti-Ro-52 were associated with photosensitivity and pulmonary disorders, respectively, in dermatomyositis. Anti-Jo-1 was significantly correlated with pulmonary disorders in polymyositis. Moreover, anti-Ro-52 was associated with anti-Jo-1 in both diseases. No significant correlation was observed between the remaining autoantibodies and the clinical and/or laboratory findings. CONCLUSIONS: Our data are consistent with those from other published studies involving other populations, although certain findings warrant consideration. Anti-Ro-52 and anti-Jo-1 were strongly associated with one another. Anti-Ro-52 was correlated with pulmonary disorders in dermatomyositis, whereas anti-Jo-1 was correlated with pulmonary alterations in polymyositis.