VILMA DOS SANTOS TRINDADE VIANA
Projetos de Pesquisa
Unidades Organizacionais
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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- 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.
- IL-23/Th17 axis is not influenced by TNF-blocking agents in ankylosing spondylitis patients(2016) MILANEZ, Fernanda Manente; SAAD, Carla G. S.; VIANA, Vilma T.; MORAES, Julio C. B.; PERICO, Gregory Vinicius; SAMPAIO-BARROS, Percival Degrava; GONCALVES, Celio R.; BONFA, EloisaBackground: Advances in pathophysiology and treatment of ankylosing spondylitis (AS) was recently demonstrated. However, the effect of anti-TNF in the newly described inflammatory pathways involved pathogenesis of this disease remains to be determined. The aim of our study was, therefore, to investigate long-term influence of anti-TNF drugs in IL-23/IL-17 axis of AS patients and their possible correlation with treatment, clinical, laboratory and radiographic parameters. Methods: Eighty-six AS anti-TNF naive patients, 47 referred for anti-TNF therapy (active-AS; BASDAI >= 4) and 39 with BASDAI < 4 (control-AS) were included. The active group was evaluated at baseline, 12-months and 24-months after TNF blockade and compared at baseline to control-AS group and to 47 healthy age-and gender-matched controls. Plasma levels of IL-17A, IL-22, IL-23 and PGE2 were measured. Non-steroidal anti-inflammatory drugs (NSAIDs) intake were recorded every 6 months. Radiographic severity and progression was assessed by mSASSS at baseline and 24 months after therapy. Results: At baseline, active-AS group presented higher IL-23 and PGE2 levels compared to control-AS group (p < 0.001 and p = 0.008) and to healthy controls (p < 0.001 and p = 0.02). After 24-months of TNF blockade, IL-23 and PGE2 remained elevated with higher levels compared with the healthy group (p < 0.001 and p = 0.03) in spite of significant improvements in all clinical/inflammatory parameters (p < 0.001). Further analysis of 27 anti-TNF-treated patients who achieved a good response (ASDAS-CRP < 2.1, with a drop >= 1.1) at 24-months revealed that IL-23 plasma levels remained higher than healthy controls (p < 0.001) and higher than control-AS group with similar disease activity (ASDAS-CRP < 2.1, p = 0.01). In active-AS group (n = 47), there was a strong correlation between IL-23 and IL-17A at baseline, 12-months and 24-months after anti-TNF therapy (p <= 0.001). Conclusion: This study provides novel data demonstrating that the IL-23/IL-17 axis is not influenced by TNF blockade in AS patients despite clinical and inflammation improvements and NSAID intake.
- Anti-ribosomal P protein: a novel antibody in autoimmune hepatitis(2013) CALICH, Ana L.; VIANA, Vilma S. T.; CANCADO, Eduardo; TUSTUMI, Francisco; TERRABUIO, Debora R. B.; LEON, Elaine P.; SILVA, Clovis A.; BORBA, Eduardo F.; BONFA, EloisaBackground Autoantibodies to ribosomal P proteins (anti-rib P) are specific serological markers for systemic lupus erythematosus (SLE) and are associated with liver involvement in this disease. The similarity in autoimmune background between autoimmune hepatitis (AIH) and SLE-associated hepatitis raises the possibility that anti-rib P antibodies might also have relevance in AIH. Aims To evaluate the frequency and clinical significance of anti-rib P antibodies in a large AIH cohort. Methods Sera obtained at diagnosis of 96 AIH patients and of 82 healthy controls were tested for IgG anti-ribosomal P protein by ELISA. All of the sera were also screened for other lupus-specific autoantibodies, three patients with the presence of anti-dsDNA (n=1) and anti-Sm (n=2) were excluded. Results Moderate to high titres (>40U) of anti-rib P antibody were found in 9.7% (9/93) of the AIH patients and none of the controls (P=0.003). At presentation, AIH patients with and without anti-rib P antibodies had similar demographic/clinical features, including the frequency of cirrhosis (44.4 vs. 28.5%, P=0.44), hepatic laboratorial findings (0.05). Importantly, at the final observation (follow-up period 10.2 +/- 4.9years), the AIH patients with anti-rib P had a significantly higher frequency of cirrhosis compared with the negative group (100 vs. 60%, P=0.04). Conclusion The novel demonstration of anti-rib P in AIH patients without clinical or laboratory evidence of SLE suggests a common underlying mechanism targeting the liver in these two diseases. In addition, this antibody appears to predict the patients with worse AIH prognoses.
- Juvenile idiopathic arthritis activity and function ability: deleterious effects in periodontal disease?(2016) PUGLIESE, Camila; VINNE, Roberta T. A. van der; CAMPOS, Lucia M. A.; GUARDIEIRO, Priscila R.; SAVIOLLI, Cynthia; BONFA, Eloisa; PEREIRA, Rosa M. R.; VIANA, Vilma S.; BORBA, Eduardo F.; SILVA, Clovis A.The impact of juvenile idiopathic arthritis (JIA) in periodontal diseases is controversial probably due to gender and age heterogeneity. We therefore evaluated a homogeneous female post-pubertal JIA population for these conditions. Thirty-five JIA patients and 35 gender/age comparable healthy controls were evaluated according to demographic data, complete periodontal evaluation, fasting lipoproteins, and anti-lipoprotein lipase antibodies. JIA scores, laboratorial tests, X-rays, and treatment were also assessed. Current age was similar in JIA patients and controls (11.90 +/- 2.0 vs. 12.50 +/- 3.0 years, p=0.289). Complete periodontal assessments revealed that gingival index, dental plaque, gingival bleeding, and clinical dental attachment indices were alike in JIA patients and controls (p>0.05), except for gingival enlargement in former group (p<0.0001). Further analysis of patients with and without gingivitis revealed that cyclosporine use was more often observed in JIA patients with gingivitis (37 vs. 0 %, p=0.01), whereas no differences were evidenced in demographic, JIA scores, inflammatory markers, and lipid profile in both groups. Of note, two parameters of periodontal assessment were correlated with JIA scores [gingival index (GI) and Childhood Health Assessment Questionnaire (CHAQ) (r(s)=+0.402, p=0.020)] and plaque index (PI) and visual analog scale (VAS) physician (r(s)=+0.430, p=0.013). In addition, evaluation of dental assessment demonstrated that JIA activity scores had positive correlation with decayed, missing, and filled teeth (DMF-T) and junvenile athritis disease activity score (JADAS) (r(s)=+0.364, p=0.037), VAS physician (r(s)=+0.401, p=0.021) and VAS patient (r(s)=+0.364, p=0.037). We demonstrated, using rigorous criteria, that periodontal and dental condition in JIA is similar to controls. In spite of that, the finding of a correlation with disease parameters provides additional evidence that increased activity and reduced functional ability underlies the deleterious effect of JIA in oral health.
- 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.
- Persistent Periodontal Disease Hampers Anti-Tumor Necrosis Factor Treatment Response in Rheumatoid Arthritis(2012) SAVIOLI, Cynthia; RIBEIRO, Ana Cristina M.; FABRI, Gisele Maria Campos; CALICH, Ana Luisa; CARVALHO, Jozelio; SILVA, Clovis A.; VIANA, Vilma S. T.; BONFA, Eloisa; SIQUEIRA, Jose Tadeu T.Objective: This study aimed to evaluate prospectively the influence and the evolution of periodontal disease (PD) in rheumatoid arthritis (RA) patients submitted to anti-tumor necrosis factor (TNF) therapy. Methods: Eighteen patients with RA (according to the American College of Rheumatology criteria) were assessed for PD before (BL) and after 6 months (6M) of anti-TNF treatment: 15 infliximab, 2 adalimumab, and 1 etanercept. Periodontal assessment included plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level. Rheumatologic evaluation was performed blinded to the dentist's assessment: demographic data, clinical manifestations, and disease activity (Disease Activity Score using 28 joints [DAS28], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]). Results: The median age and disease duration of patients with RA were 50 years (25-71 y) and 94% were female. Periodontal disease was diagnosed in 8 patients (44.4%). Comparing BL to 6M, periodontal parameters in the entire group remained stable (P > 0.05) throughout the study (plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level), whereas an improvement in most analyzed RA parameters was observed in the same period: DAS28 (5.5 vs. 3.9, P = 0.02), ESR (21 vs. 12.5 mm/first hour, P = 0.07), and CRP (7.8 vs. 2.8 mg/dL, P = 0.25). Further analysis revealed that this improvement was restricted to the group of patients without PD (DAS28 [5.5 vs. 3.6, P = 0.04], ESR [23.0 vs. 11.5 mm/first hour, P = 0.008], and CRP [7.4 vs. 2.1, P = 0.01]). In contrast, patients with PD had lack of response, with no significant differences in disease activity parameters between BL and 6M: DAS28 (5.2 vs. 4.4, P = 0.11), ESR (17.0 vs. 21.0, P = 0.56), and CRP (9.0 vs. 8.8, P = 0.55). Conclusions: This study supports the notion that PD may affect TNF blocker efficacy in patients with RA. The possibility that a sustained gingival inflammatory state may hamper treatment response in this disease has high clinical interest because this is a treatable condition.
- The clinical utility of anti-ribosomal P autoantibodies in systemic lupus erythematosus(2014) PASOTO, Sandra Gofinet; VIANA, Vilma Santos Trindade; BONFA, EloisaSystemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect multiple organs and thus has a large spectrum of clinical presentations. Assessment of the autoantibody profile is fundamental for the clinical management of SLE patients, providing important data for diagnosis, clinical characterization and disease activity evaluation. Anti-ribosomal P protein (anti-Rib-P, anti-P) antibody, described in the 1980s, is a serological marker for SLE that is present in 13-20% of cases. This reactivity was initially thought to be associated with neuropsychiatric involvement in SLE, with certain conflicting results. Subsequently, associations of anti-Rib-P with liver and renal involvement in lupus were reported. Recently, anti-Rib-P was detected in autoimmune hepatitis patients. Anti-Rib-P reactivity to Trypanosoma cruzi ribosomal target antigens in patients with Chagas heart disease has also been described. This review focuses on the usefulness of the determination of anti-Rib-P in SLE and in other autoimmune and non-autoimmune disorders in clinical practice.
- Antibodies to ribosomal P proteins in lupus nephritis: A surrogate marker for a better renal survival?(2011) MACEDO, Patricia Andrade de; BORBA, Eduardo Ferreira; VIANA, Vilma dos Santos Trindade; LEON, Elaine Pires; TESTAGROSSA, Leonardo de Abreu; BARROS, Rui Toledo; NASCIMENTO, Ana Patricia; BONFA, EloisaObjective: To define if antibodies to ribosomal P proteins disclose a better lupus nephritis long-term survival. Methods: Sixty consecutive SLE patients with biopsy-proven nephritis (2004 ISN/RPS) were evaluated for renal survival parameters. Inclusion criteria were at least one serum sample at: renal flares, biopsy, and last follow-up until 2008. Anti-P was detected by ELISA/immunoblot and anti-dsDNA by indirect immunofluorescence/ELISA. Results: Eleven patients (18%) with anti-P+ (without anti-dsDNA) during renal flare were compared to 49 (82%) persistently negative for anti-P throughout the study. At the final follow-up post-biopsy (6.3 +/- 2.5 vs. 6.8 +/- 2.4 years, p = 0.36), the comparison of anti-P+/anti-dsDNA with anti-P group revealed a trend to lower mean creatinine levels (0.9 +/- 0.3 vs. 2.3 +/- 2.1 mg/dl, p = 0.07), lower frequency of dialysis (0% vs. 35%, p = 0.025), and higher frequency of normal renal function (91% vs. 53%, p = 0.037). The overall renal survival was significantly higher in anti-P+/anti-dsDNA compared to anti-P (11.0 +/- 4.5 vs. 9.2 +/- 4.5 years, p = 0.033), anti-dsDNA+/anti-P (vs. 8.7 +/- 4.7 years, p = 0.017), and anti-P /anti-dsDNA (vs. 9.8 +/- 4.3 years, p = 0.09) groups. Conclusion: Our data supports the notion that anti-P antibody in the absence of anti-dsDNA during nephritis flares is a valuable marker to predict a better long-term renal outcome in lupus patients.
- 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.