SANDRA GOFINET PASOTO
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/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
conferenceObject Peripheral Neuropathy Due to Systemic Lupus Erythematosus (SLE) Itself: Incidence, Disease Risk Factors and Outcome(2012) FARGETTI, Simone; SHINJO, Samuel K.; PASOTO, Sandra G.; CALICH, Ana L.; BONFA, Eloisa; BORBA, Eduardo F.Background/Purpose: Peripheral neuropathy (PN) solely attributable to SLE itself is difficult to define since most of these patients are exposed to several other conditions that may cause this manifestation. The aim is to determine characteristics and outcome of PN attributed exclusively to SLE and its possible association with clinical/laboratorial features in a large cohort. Methods: SLE patients (ACR 1997) with PN were identified from our Lupus Outpatient Clinic computerized database of 1038 patients. Only patients with definitive PN proved by electroneuromyography were included. Exclusion criteria were conditions related to PN: diabetes mellitus, alcohol consumption, use of any drug related to neuropathy (thalidomide, statins, etc.), thyroid disease, infection, cancer, vitamin B12 deficiency, renal or hepatic failure, and other autoimmune disease (antiphospholipid syndrome, Sjogren’s syndrome, etc.). Medical records were extensively reviewed and included clinical/laboratorial data, treatment, and evolution. Each SLE patient with PN [n 22] was compared with 2 SLE patients without PN (controls) [n 44] that were age- and sex-matched and had similar disease duration. Results: PN exclusively attributed to SLE was identified in 22 patients (2.1%). The mean age (34.4 11.6 vs. 33.9 9.6 years, p 0.85) and disease duration (9.2 7.7 vs. 9.9 6.8 years, p 0.73) of PN were similar to controls. The interval between SLE onset and PN diagnosis was 4.9 5.7 years and the mean SLEDAI scores was higher in PN patients (5.4 7.6 vs. 1.8 2.9,p 0.001). The most common pattern on electroneuromyography was sensorimotor polyneuropathy of lower limbs (50%), followed by monon-europathy (26.9%), and polyradiculoneuropathy (15.3%). PN was associated to hematological involvement (72.7% vs. 43.2%,p 0.036), leukopenia (50% vs. 20.5%,p 0.022), lymphopenia (68.2% vs. 29.5%,p 0.004), cutaneous vasculitis (54.5% vs. 22.7%,p 0.014), and anti-Sm (50% vs. 15.9%,p 0.007). Multivariate analysis revealed that PN was related to anti-Sm (OR 5.36; 95%CI 1.37–20.99) and cutaneous vasculitis (OR 4.97; 95%CI 1.23–20.08). All SLE patients received corticosteroids, most of them associated with immunosuppressive drug (59% cyclophosphamide; 31.8% azathioprine). After immunosuppressive therapy, 63.6% improved of neurological symptoms and 31.8% remained stable. Conclusion: Our study suggested that PN attributed to SLE itself is rare in the absence of other conditions and seems to be strongly associated to anti-Sm antibodies and cutaneous vasculitis. A favorable outcome with immunosuppressive therapy is observed in most of SLE patients with this neurological manifestation.- Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?(2012) BORBA, Eduardo F.; SAAD, Carla G. S.; PASOTO, Sandra G.; CALICH, Ana L. G.; AIKAWA, Nadia E.; RIBEIRO, Ana C. M.; MORAES, Julio C. B.; LEON, Elaine P.; COSTA, Luciana P.; GUEDES, Lissiane K. N.; SILVA, Clovis A. A.; GONCALVES, Celio R.; FULLER, Ricardo; OLIVEIRA, Suzimara A.; ISHIDA, Maria A.; PRECIOSO, Alexander R.; BONFA, EloisaObjective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) epsilon 20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED epsilon 20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED epsilon 20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED epsilon 20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED epsilon 20 mg + IS + CQ (57.4%; P = 0.09). Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity.
conferenceObject Long-Term Changes in Autoantibody Profile After Pandemic Unadjuvanted Influenza A/H1N1 Vaccine in Sjogren's Syndrome(2012) PASOTO, Sandra G.; RIBEIRO, Ana C.; VIANA, Vilma S. T.; LEON, Elaine P.; BUENO, Cleonice; NETO, Mauricio Levy; PRECIOSO, Alexander R.; TIMENETSKY, Maria do Carmo S.; BONFA, EloisaBackground/Purpose: Despite WHO recommendations about the A/California/7/2009/H1N1-like virus vaccination, there are no studies evalu- ating its possible influence on clinical manifestations and autoantibody profile in (primary) Sjögren’s syndrome (SS). Objectives: To evaluate short/long-term effect of influenza A/California/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS. Methods: Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 gender-, age-, matched-healthy controls were evaluated before and 21-days after vaccination with unadjuvanted influenza A/H1N1-like virus regarding seroprotection/seroconversion, factor increase in geometric mean titre (FI-GMT) and side effects. New onset of parotiditis, arthritis, vasculitis, pneumonitis or neurological disorders and autoantibody profile [antinuclear antibodies (ANA), rheumatoid factor (RF), anti-dsDNA, anti-Ro(SS-A)/La(SS-B), anti-alpha-fodrin, anti-RNP, anti-Sm and anticar-diolipin] were assessed before, 21-days and 1-year after vaccination. Results: Patients and controls had similar rates of seroconversion (78 vs. 69%, p=0.42), seroprotection (83 vs. 72%, p=0.26) and FI-GMT (p=0.85). Pre-vaccination evaluation revealed that disease duration, glucocorticoid (mean dose 10.15.1 mg/day), methotrexate (up to 17.5 mg/week) or azathioprine (up to 100 mg/day) did not affect seroconversion (p> 0.05). Regarding short-term analysis, no change in the frequency or levels of autoantibodies was observed (p>0.05) and only mild side effects were observed in comparable rates to controls (p> 0.05). At 1-year follow-up, the rate of new disease flares was similar to the previous year (11 vs. 19%, p 0.51) and four seroconverted patients developed positivity to one of the following specificities: anti-Ro/SS-A, anti-La/SS-B, anti-alpha-fodrin, or IgM anticardiolipin. None developed other specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SS-A (p< 0.0001) and anti-La/SS-B (p< 0.002) was detected after 1-year with no change in the other autoantibodies. Conclusion: This is the first study to indicate that influenza A/H1N1 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.- Osteoporotic hip fractures in non-elderly patients: relevance of associated co-morbidities(2012) PASOTO, Sandra G.; YOSHIHARA, Liz A. K.; MAEDA, Lucy C.; BERNIK, Marcia M. S.; LOTUFO, Paulo A.; BONFA, Eloisa; PEREIRA, Rosa M. R.Osteoporotic hip fractures (OHF) are not limited to elderly; however, studies in non-elderly are scarce. Thus, the aim of this study was to evaluate co-morbidities in non-elderly patients with OHF in a Community Teaching Hospital. All hospitalizations due to OHF during a 3-year period in a Community Teaching Hospital were retrospectively evaluated for co-morbidities, and patients 18-64 years old were compared with those a parts per thousand yen65 years old. Of all hospitalizations, 232 (0.73%) were due to hip fractures, and 120/232 (51.7%) patients had OHF. The comparison of the 13 (10.8%) OHF patients < 65 years old (47.3 +/- A 9.7 years) with 107 (89.2%) a parts per thousand yen65 years old (80.4 +/- A 7.7 years) revealed a male predominance (61.5 vs. 27.1%, P = 0.022) and a distinct ethnic distribution with a lower proportion of Caucasians in the former (61.5 vs. 86.9%, P = 0.033). Moreover, non-elderly OHF patients had higher frequencies of insulin-dependent DM (38.5 vs. 3.7%, P = 0.001) and alcoholism (38.5 vs. 4.7%, P = 0.001) than aged patients. In contrast, rates of age-related co-morbidities such as stroke (7.7 vs. 18.7%, P = 0.461), heart failure (23.1 vs. 14.0%, P = 0.411), and dementia (7.7 vs. 15.9%, P = 0.689) were comparable in both groups. Logistic regression analysis demonstrated that insulin-dependent DM (OR = 25.4, 95% CI = 4.7-136.8, P < 0.001) and alcoholism (OR = 20.3, 95% CI = 3.9-103.3, P < 0.001) remained as independent risk factors for OHF in non-elderly patients. Osteoporosis is an important cause of HF in Community Hospital. Non-elderly patients with OHF have a peculiar demographic profile and associated co-morbidities. These findings reinforce the need of early osteoporosis diagnosis and rigorous fracture prevention in patients with DM and alcoholism.
conferenceObject IS H1N1 INFLUENZA VACCINE SAFE AND EFFECTIVE IN PATIENTS WITH SSc?(2012) ANDRADE, D.; SEGURO, L.; RIBEIRO, A.; MORAES, J.; SAAD, C.; AIKAWA, N.; CALICH, A.; VIANA, V.; PASOTO, S.; LEVY-NETO, M.; LAURINDO, I.; TIMENESTSKY, M.; PRECIOSO, A.; BONFA, E.; SAMPAIO-BARROS, P.Introduction. Immunosuppressed patients are potentially at risk to suffer from life-threatening pulmonary infections caused by H1N1. Although pulmonary disease is an important cause of morbidity in patients with SSc, low rates of influenza vaccination are still observed in this population due to lack of information and fear of adverse events. The recent WHO recommendation that the 2010–2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus reinforces the need to access the safety and efficacy of H1N1 vaccination in SSc patients. Patients and methods. One hundred twenty-seven patients and 234 controls were vaccinated with adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. All participants were evaluated pre- and 21 days post-vaccination and serology for anti-H1N1 was performed by haemagglutination inhibition (HI) assay (HIA). Efficacy was assessed by seroprotection and seroconversion rates and the factor increase in geometric mean antibody titre (GMT). Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. Severe side effects were considered if hospitalization was required. Results. SSc patients had mean age of 52 (5.3) years, mean disease duration of 11.96 (7.9) years and a female predominance (93%). Of SSc patients, 69.3% had limited cutaneous disease, whereas 30.7% had diffuse cutaneous disease. Half of the patients were on immunosuppressant therapy (mostly AZA, MTX and CYC). Thirteen (10%) patients were taking CSs, but only two patients received a daily dose > 10 mg of prednisone. SSc patients and controls presented similar pre-vaccination GMT (11.2 vs 9.3; P = 0.094) and seroprotection rates (18.1 vs. 11.5%; P = 0.110). After vaccination seroprotection rates (81.1 vs 82.9%; P = 0.668) and GMT (134.4 vs. 122.9; P = 0.654) rose in both groups. Seroconversion rates (72.4 vs 76.9%; P = 0.372) and factor increase in GMT (12.0 vs 13.2; P = 0.553) were comparable in both groups. Disease-modifying antirheumatic drugs were not associated with reduced vaccination responses (P > 0.05). Immunization was well tolerated with mild local (7.1 vs 14.1%; P = 0.058) and minor systemic reactions (23.6 vs 25.6%; P = 0.704) in patients and controls, respectively. No severe side effect was reported.Conclusion. Vaccination against H1N1 was safe and induced a satisfactory response in patients with SSc, including in those under immunosuppressive therapy. Due to the inherent risks of lower respiratory infections in this group of patients, physicians should consider annually influenza vaccination recommendation.- Lupus anticoagulant: a marker for stroke and venous thrombosis in primary Sjogren's syndrome(2012) PASOTO, Sandra Gofinet; CHAKKOUR, Henrique Pires; NATALINO, Renato Romera; VIANA, Vilma S. T.; BUENO, Cleonice; LIANZA, Alessandro Cavalcanti; ANDRADE, Jose Lazaro de; LEVY NETO, Mauricio; FULLER, Ricardo; BONFA, EloisaAntiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) have been described in primary Sjogren's syndrome (pSS) with controversial findings regarding aPL prevalence and their association with thrombotic events. We evaluated 100 consecutive pSS patients (American-European criteria) and 89 age-gender-ethnicity-matched healthy controls for IgG/IgM anticardiolipin (aCL), IgG/IgM anti-beta2-glycoprotein-I (a beta 2GPI), and lupus anticoagulant (LA) (positivity according to APS Sydney's criteria). Clinical analysis followed standardized interview and physical examination assessing thrombotic and nonthrombotic APS manifestations and thrombosis risk factors. aPLs were detected in 16 % patients and 5.6 % controls (p = 0.035). LA was the most common aPL in patients (9 %), followed by a beta 2GPI (5 %) and aCL (4 %). Thrombotic events occurred in five patients [stroke in two, myocardial infarction in one and deep-vein thrombosis (DVT) in four], but in none of controls (p = 0.061). Mean age at time of stroke was 35 years. Three patients with thrombotic events (including the two with stroke) had APS (Sydney's criteria) and were positive exclusively for LA. Comparison of patients with (n = 16) and without (n = 84) aPL revealed similar mean age, female predominance, and ethnicity (p > =0.387). Frequencies of livedo reticularis (25 vs. 4.8 %, p = 0.021), stroke (12.5 vs. 0 %, p = 0.024), and DVT (18.8 vs. 1.2 %, p = 0.013) were significantly higher in APL + patients. Conversely, frequencies of hypertension, dyslipidemia, diabetes, obesity, smoking, sedentarism, and hormonal contraception were similar in patients with or without aPL (p a parts per thousand yenaEuro parts per thousand 0.253). Our study identified LA as an important marker for APS in pSS, particularly for stroke in young patients, warranting routine evaluation of these antibodies and rigorous intervention in modifiable risk factors.
conferenceObject Altered Circulating Follicular Helper T Cell Phenotype and Subset Composition Are Associated with Disease Activity in Patients with Systemic Lupus Erythematosus(2012) HO, Hsi-en; CHOI, Jin Young; BUNIN, Viviane M.; PASOTO, Sandra G.; CARRASCO, Solange; BORBA, Eduardo F.; GONCALVES, Celio R.; COSTA, Priscila R.; KALLAS, Esper G.; BONFA, Eloisa; CRAFT, Joseph E.Background/Purpose: Autoreactive B cells in SLE undergo autoantigen selection, suggesting a requirement for germinal center follicular helper T (Tfh) cells in their maturation. However, evidence for dysregulation of Tfh cells in SLE and their potential contribution to disease remains unclear. Recently, blood CXCR5 CD4 T cells, a heterogeneous pool consisting of functionally distinct Th1-, Th2-, and Th17-like subsets, have been proposed to be the circulating counterpart of Tfh (cTfh) cells. We now ask if changes in cTfh markers or subset composition within blood CXCR5 cells are found in SLE patients, and the extent to which such alterations are associated with B cell and disease activity. Methods: Blood samples from 49 clinically well-characterized SLE patients, 28 Behc ̧et’s disease (BD) patients, and 16 healthy controls were included. Expression of Tfh surface markers (CXCR5; ICOS, inducible T-cell costimulator; PD-1, programmed cell death protein-1), composition of blood CXCR5 subsets, and frequency of plasmablasts were enumerated by flow cytometry. The phenotype of blood CXCR5 subsets was correlated with disease activity, clinical history, and plasmablast expansion. Results: SLE patients had significant expansion of CXCR5 ICOS PD-1 CD4 T cells compared to controls (p 0.001). PD-1, but not ICOS or CXCR5, expression was markedly elevated in CD4 T cells of SLE patients compared to BD patients and healthy controls (p 0.001). PD-1 MFI in CXCR5 cells correlated with SLE disease activity index (SLEDAI; Spearman r 0.43, p 0.03). PD-1 MFI also correlated with expansion of plasmablasts (Spearman r 0.34, p 0.02). In SLE patients with high anti-dsDNA antibody titers, PD-1 expression in CXCR5cells was also significantly elevated compared to patients with no detectable titers (p 0.004). Enhanced PD-1 expression was neither a function of disease duration nor past activity; rather, it reflected current disease activity. Compared to BD patients, SLE patients also had an increase in the CXCR5 Th2 (p 0.05) and a decrease in the Th17 (p 0.001) subsets. Concurrently, PD-1 expression in SLE patients was significantly higher in CXCR5 Th2 cells compared to Th17 cells (p 0.01). The expansion of the CXCR5 Th2 subset was also positively associated with SLEDAI scores. Conclusion: Our results demonstrate that dysregulation of cTfh cells is strongly correlated with disease activity in SLE, supporting a potential causal relationship. The altered composition of blood CXCR5 cells also appeared to be a fundamental cellular defect in SLE, with our results revealing a novel dimension of Tfh dysregulation that may be central to disease pathogenesis.- Seizures in Primary Antiphospholipid Syndrome: The Relevance of Smoking to Stroke(2012) CARVALHO, Jozelio Freire de; PASOTO, Sandra Gofinet; APPENZELLER, SimoneObjectives. To evaluate the frequency of seizures in primary antiphospholipid syndrome (PAPS) and their possible clinical and laboratory associations. Methods. Eighty-eight PAPS patients (Sydney's criteria) were analyzed by a standard interview, physical examination and review of medical charts. Risk factors for seizures, clinical manifestations, associated comorbidities, and antiphospholipid antibodies were evaluated. Results. Nine (10.2%) patients with seizures were identified, 77.8% had convulsions onset after PAPS diagnosis. Mean age, gender, and race were comparable in groups with or without seizures. Interestingly, a higher frequency of current smoking (44.4 versus 10.1%, P = 0.019) was observed in the first group. Stroke, Sneddon's syndrome, and livedo reticularis were more frequent in PAPS patients with seizures than those without seizures, although not statistically significant (P > 0.05). Comparison between patients with seizures onset after PAPS diagnosis (n = 7) and those without convulsions (n = 79) demonstrated a higher frequency of current smoking (42.9 versus 10%, P = 0.042) and stroke in the first group (71.4 versus 30.4%, P = 0.041). Regression analysis confirmed that smoking (P = 0.030) and stroke (P = 0.042) were independently associated to seizures. Conclusion. About 10.2% of PAPS patients had convulsions, predominantly after PAPS diagnosis, and seizures were associated to current smoking and stroke.