VILMA DOS SANTOS TRINDADE VIANA
Projetos de Pesquisa
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LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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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.- 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.
article 17 Citação(ões) na Scopus Reduction of ovarian reserve in adult patients with dermatomyositis(2015) SOUZA, F. H. C. de; SHINJO, S. K.; YAMAKAMI, L. Y. S.; VIANA, V. S. T.; BARACAT, E. C.; BONFA, E.; SILVA, C. A.Objective To assess ovarian reserve markers and anti-corpus luteum (anti-CoL) antibodies in dermatomyositis (DM) patients. Methods Forty female DM patients were invited to participate. Exclusion criteria included hormonal contraceptive use within the last six months, neoplasia associations, overlapped systemic autoimmune diseases, current pregnancy, gynaecological surgery and individual choice not to participate. The final experimental group for this cross-sectional study included 16 DM patients and 23 healthy controls, each of whom was evaluated during the early follicular phase of the menstrual cycle. Values for IgG anti-CoL (via immunoblotting), follicle stimulating hormone (FSH), estradiol, inhibin B, anti-Mullerian hormone (AMH) serum levels (via ELISA) and sonographic antral follicle count (AFC) were determined. Results DM patients and controls were of comparable mean age (p>0.05). The mean age of DM onset was 29.1 +/- 4.7 years, with disease duration of 5.6 +/- 3.2 years. Menstrual cycle characteristics, comorbidity and lifestyle were similar amongst patients in both groups (p>0.05). AMH values of <= lng/mL (p=0.027) and AFC values (p=0.017) were significantly reduced in DM patients relative to the control group, whereas serum estradiol levels (p<0.001) were higher in DM patients compared to controls. In contrast, serum FSH and inhibin B levels, ovarian volumes, and anti-CoL antibody frequency were similar in both groups. Differences in AFC and estradiol were determined to be significant following Bonferroni correction for multiple testing. Conclusion We identified a diminished ovarian reserve in DM patients of reproductive age. Further studies are necessary to assess the idiopathic inflammatory myopathy-related factors involved in the ovarian impairment of this patient population.- SYSTEMIC SCLEROSIS-RELATED AUTO-ANTIBODIES ARE MARKERS OF NEW CLINICAL ASSOCIATIONS IN A COHORT OF 328 BRAZILIAN PATIENTS(2014) SILVA, C. M.; BORTOLUZZO, A. B.; VIANA, V. S.; PASOTO, S. G.; LEON, E. P.; BONFA, E.; SAMPAIO-BARROS, P. D.
conferenceObject TESTICULAR SERTOLI CELL FUNCTION IN ANKYLOSING SPONDYLITIS: THE POSSIBLE EFFECT OF TNF BLOCKAGE(2012) SAAD, C. G. S.; ALMEIDA, B. P. de; SOUZA, F. H. C.; MORAES, J. C. B.; NUKUMIZU, L. A.; SAMPAIO-FARROS, P. D.; VIANA, V. S. T.; BONFA, E.; SILVA, C. A.Introduction: Inhibin B is an important testicular Sertoli cell function marker allowing a global evaluation of testicular tissue. However there are no data regarding this cell function in ankylosing spondylitis (AS) patients.in this hormone production. Materials and Methods: 20 consecutive male AS patients and 24 healthy controls were evaluated. At study entry, AS patients were not receiving sulfasalazine/methotrexate and they never used biological/cytotoxic agents. Serum dimeric inhibin B levels were measured by a double-antibody ELISA. Demographic, disease parameters and urologic evaluation were systematically performed. The latter included testicular Döppler ultrasound, hormone profile and semen analysis. Ten of these patients received anti-TNF treatment and they were re-evaluated for inhibin B and disease parameters at 6 months(6M). Four of them also repeated sperm analysis. Results: At study entry, the median of current and spermarche age were similar in AS patients and controls [33(17-53) vs. 28.5(15-54) years, p=0.175; 13(9-18) vs. 12(11-15)years, p=0.358; respectively]. The median of inhibin B [68(23-265) vs. 112.9(47.8-231.9)pg/mL, p=0.111], FSH levels and the other hormones were comparable in both groups (p>0.05). All patients and controls had normal sperm motility and concentration with two AS patients presenting borderline low inhibin B levels. Further analysis at 6M of the 10 patients referred for anti-TNF therapy, including one with borderline inhibin B, revealed that median inhibin B levels remained largely stable [126.5(24-316) vs. 116.5(28-265)pg/mL, p=0.431]. Sperm motility/concentration were preserved in the four patients that performed this analysis after anti-TNF. Conclusions: This is the first study to demonstrate, through a specific marker, a normal testicular Sertoli cell function associated with preserved sperm quality in AS patients. We further identified that anti-TNF drugs do not seem to have a deleterious effect in inhibin B production reinforcing its safety for testicular function in this disease.- CLINICAL AND SEROLOGICAL COMPARATIVE ANALYSIS OF SYSTEMIC SCLEROSIS WITH OR WITHOUT OVERLAP SYNDROMES IN A LARGE BRAZILIAN COHORT(2014) SILVA, C. M.; VIANA, V. S.; PASOTO, S. G.; SEGURO, L. P.; ANDRADE, D. C. O.; BONFA, E.; SAMOIO-BARROS, P. D.
- 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).
- Electrophysiological dysfunction induced by anti-ribosomal P protein antibodies injection into the lateral ventricle of the rat brain(2017) GABURO JR., N.; CARVALHO, J. Freire de; TIMO-IARIA, C.; BUENO, C.; REICHLIN, M.; VIANA, V. S. T.; BONFA, E.Objective: Anti-ribosomal P antibodies (anti-P) are strongly associated with neuropsychiatric lupus. This study was designed to determine whether these antibodies are capable of causing electro-oscillogram (EOSG) and behavior alterations in rats. Methods: IgG fraction anti-P positive and affinity-purified anti-P antibodies were injected intraventricularly in rats. Sequential cortical and subcortical EOSGs were analyzed during 30 days. IgG anti-Ro/SS-A and normal IgG were used as controls. Results: All 13 animals injected with IgG anti-P demonstrated a high prevalence of polyspikes, diffusely distributed in hippocampal fields and cerebral cortex. These abnormalities persisted approximately a month. Remarkably, an identical electrical disturbance was observed with the inoculation of affinity-purified anti-P antibodies. The EOSG alterations were associated with behavioral disorders with varying degrees of severity in every animal injected with anti-P. In contrast, no changes in EOSG or behavioral disturbances were observed in the control group. Conclusion: Our study indicates that anti-P antibodies can directly induce electrophysiological dysfunction in central nervous system particularly in hippocampus and cortex associated with behavior disturbances.