VILMA DOS SANTOS TRINDADE VIANA
Projetos de Pesquisa
Unidades Organizacionais
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- 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.
- 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.
- Antibodies to cellular prion protein and its cognate ligand stress-inducible protein 1 in systemic lupus erythematosus(2020) CARVALHO, Jozelio F.; VIANA, Vilma S. T.; LEON, Elaine P.; BONFA, Eloisa; PASOTO, Sandra G.; MARTINS, Vilma R.Objectives This study aimed to determine the prevalence of autoantibodies to cellular prion protein (PrP(C)) and its cognate ligand stress-inducible protein 1 (STI-1) in sera from patients with systemic lupus erythematosus (SLE), and their possible correlation with clinical and serological SLE manifestations. Methods Sera were obtained from 103 consecutive SLE patients and 77 healthy controls. IgG antibodies to PrP(C) and to STI-1 were determined by ELISA using recombinant purified proteins, and the reactivities were confirmed by immunoblotting. A panel of lupus-related autoantibodies was investigated by well-standardized techniques. Clinical data were obtained by extensive chart review, and disease activity was scored using the SLE Disease Activity Index (SLEDAI). Results The frequency of anti-PrP(C) antibodies in SLE (7.8%) was similar to healthy controls (p = 0.56), but these antibodies were significantly associated with previous central nervous system (CNS) involvement when compared with patients without anti-PrP(C) (33.3% vs. 7.5%;p = 0.04). On the other hand, anti-STI-1 reactivity was more frequently observed in SLE patients than in healthy controls (12.6% vs. 2.6%;p = 0.026), and this reactivity was associated with a lower frequency of renal disease (23.1% vs. 54.4%;p = 0.04). These two antibody specificities were not associated with SLEDAI score or with the presence of lupus autoantibodies (p > 0.05). Conclusion This is the first evidence of reactivity to PrP(C) in SLE. The intriguing association of these antibodies and previous CNS involvement raises the possibility of a pathogenic role for them in SLE CNS damage.
- RETRACTION: Antibodies to cellular prion protein and its cognate ligand stress-inducible protein 1 in systemic lupus erythematosus (Retraction of Vol 93, Pg 861, 2020)(2020) CARVALHO, J. F.; VIANA, V. S. T.; LEON, E. P.; BONFA, E.; PASOTO, S. G.; MARTINS, V. R.
- Podocyte injury in pure membranous and proliferative lupus nephritis: distinct underlying mechanisms of proteinuria?(2014) REZENDE, G. M.; VIANA, V. S.; MALHEIROS, D. M. A. C.; BORBA, E. F.; SILVA, N. A. S.; SILVA, C.; LEON, E. P.; NORONHA, I. L.; BONFA, E.Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean follow-up of four years there was a tendency toward lower mean levels of proteinuria in patients with preserved synaptopodin staining (0.26 +/- 0.23 vs. 0.84 +/- 0.90 g/24 h, p = 0.05) compared with those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and nephrin (60%) in the pure membranous group whereas only <10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome.