EDUARDO FERREIRA BORBA NETO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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- Erratic control of breathing during exercise in patients with systemic lupus erythematosus: a pilot-study(2011) PRADO, D. M. L. do; GUALANO, B.; MIOSSI, R.; LIMA, F. R.; ROSCHEL, H.; BORBA, E.; BONFA, E.; PINTO, A. L. de SaPurpose: The aim of this study was to provide a comprehensive evaluation of the pattern and timing of breathing during incremental exercise in a sample of women living with systemic lupus erythematosus (SLE). Methods: In this cross-sectional study, 20 women with SLE without pulmonary involvement were compared with 20 gender-, body mass index- (BMI), and age-matched healthy individuals. By using a cardiopulmonary incremental exercise test, the following parameters were assessed: tidal volume (VT); breathing frequency (BF); total respiratory time (TOT); inspiratory time (TI); expiratory time (TE); inspiratory time to total time (TI/TOT); mean inspiratory flow (VT/TI); ventilatory equivalent for carbon dioxide (VE/VCO(2)) and end-tidal carbon dioxide pressure (PETCO(2)). Results: BF and BF/VT were significantly higher in patients with SLE versus controls, whereas VT, TE, TI and TOT were significantly lower in the former group (p < 0.05). Additionally, patients with SLE presented higher VE/VCO(2) and lower PETCO(2) than controls (p < 0.05), suggesting a ventilatory inefficiency. Conclusion: We reported compelling evidence of abnormal pattern and timing of breathing during incremental exercise in SLE. Considering that an erratic control of breathing may play an important role in exercise intolerance and fatigue, respiratory exercises emerge as a potential treatment for these symptoms in patients with SLE. Lupus (2011) 20, 1535-1540.
- Decreased high-density lipoprotein cholesterol levels in polyarticular juvenile idiopathic arthritis(2011) MARANGONI, Roberta Goncalves; HAYATA, Andre L.; BORBA, Eduardo F.; AZEVEDO, Pedro M.; BONFA, Eloisa; GOLDENSTEIN-SCHAINBERG, ClaudiaOBJECTIVES: To investigate the prevalence of dyslipoproteinemia in a homogeneous cohort of polyarticular juvenile idiopathic arthritis patients. METHODS: Based on the National Cholesterol Education Program, fasting lipoprotein levels and risk levels for coronary artery disease were determined in 28 patients with polyarticular juvenile idiopathic arthritis. The exclusion criteria included diabetes, thyroid dysfunction, smoking, proteinuria, lipid-lowering drugs, and hormone/diuretic therapy. Disease activity, disease duration, and therapy with corticosteroids and/or chloroquine were defined at the time of lipid measurements. RESULTS: Dyslipoproteinemia was identified in 20 of the 28 (71%) patients with polyarticular juvenile idiopathic arthritis. The primary lipoprotein risk factor was decreased high-density lipoprotein cholesterol (57%), followed by elevated levels of low-density lipoprotein cholesterol (18%), triglycerides (14%), and total cholesterol (7%). The male patients had decreased high-density lipoprotein cholesterol levels than the female patients (p<0.05). The incidence of decreased high-density lipoprotein cholesterol levels did not seem to be affected by disease activity or therapy because the incidence was similar in patients with active or inactive disease, with or without corticosteroid use and with or without chloroquine use. In addition, the frequency of decreased high-density lipoprotein cholesterol levels was similar in patients with short (<= 5 years) vs. long (>5 years) disease duration. CONCLUSIONS: Dyslipoproteinemia is highly prevalent in patients with polyarticular juvenile idiopathic arthritis and is primarily related to decreased high-density lipoprotein cholesterol levels; therefore, early intervention is essential.
- Penile anthropometry in systemic lupus erythematosus patients(2011) VECCHI, A. P.; BORBA, E. F.; BONFA, E.; COCUZZA, M.; PIERI, P.; KIM, C. A.; SILVA, C. A.The aim of this study was to evaluate penile anthropometry in systemic lupus erythematosus (SLE) patients compared with healthy controls and the possible relevant pubertal, clinical, hormonal and treatment factors that could influence penile dimensions. Twenty-five consecutive SLE patients were assessed by urological examination, sexual function, testicular ultrasound, hormones, sperm analysis, genetic analysis, clinical features and treatment. The control group included 25 age-matched healthy males. SLE patients had a lower median penis length and circumference [8 (7.5-10) vs. 10 (8-13) cm, p = 0.0001; 8 (7-10) vs. 10 (7-11) cm, p = 0.001; respectively], lower median testicular volume by right and left Prader [15 (10-25) vs. 20 (12-25) ml, p = 0.003; 15 (10-25) vs. 20 (12-25) ml, p = 0.006; respectively], higher median of follicle-stimulating hormone [5.8 (2.1-25) vs. 3.3 (1.9-9) IU/l, p = 0.002] and lower morning total testosterone levels (28% vs. 0%, p = 0.009) compared with controls. In spite of that, erectile dysfunction was not observed in patients or controls. Analyses of lupus patients revealed that the median penis circumference was lower in patients with disease onset before first ejaculation compared with those with disease onset after first ejaculation [7.8 (7-10) vs. 9.0 (7.5-10) cm, p = 0.026]. No differences were observed in the median penile anthropometry regarding sexual dysfunction (p = 0.610), lower morning total testosterone levels (p = 0.662), oligo/azoospermia (p = 0.705), SLE Disease Activity Index >= 4 (p = 0.562), Systemic Lupus International Collaborating Clinics/ACR Damage Index >= 1 (p = 0.478), prednisone cumulative dose (p = 0.789) and intravenous cyclophosphamide therapy (p = 0.754). Klinefelters syndrome (46XY/47XXY) was diagnosed in one (4%) SLE patient with decreased penile size whereas Y-chromosomal microdeletions was absent in all of them. In conclusion, we have identified reduced penile dimensions in SLE patients with no deleterious effect in erectile function. Disease onset before first ejaculation seems to affect penis development in pre-pubertal lupus. Lupus (2011) 20, 512-518.
- Abnormal chronotropic reserve and heart rate recovery in patients with SLE: a case-control study(2011) PRADO, D. M. Leite do; GUALANO, B.; MIOSSI, R.; SA-PINTO, A. L.; LIMA, F. R.; ROSCHEL, H.; BORBA, E. F.; BONFA, E.Abnormal heart-rate (HR) response during or after a graded exercise test has been recognized as a strong and an independent predictor of all-cause mortality in healthy and diseased subjects. The purpose of the present study was to evaluate the HR response during exercise in women with systemic lupus erythematosus (SLE). In this case-control study, 22 women with SLE (age 29.5 perpendicular to 1.1 years) were compared with 20 gender-, BMI-, and age-matched healthy subjects (age 26.5 +/- 1.4 years). A treadmill cardiorespiratory test was performed and HR response during exercise was evaluated by the chronotropic reserve (CR). HR recovery (Delta HRR) was defined as the difference between HR at peak exercise and at both first (Delta HRR1) and second (Delta HRR2) minutes after exercising. SLE patients presented lower peak VO(2) when compared with healthy subjects (27.6 perpendicular to 0.9 vs. 36.7 perpendicular to 1.1 ml/kg/min, p = 0.001, respectively). Additionally, SLE patients demonstrated lower CR (71.8 +/- 2.4 vs. 98.2 +/- 2.6%, p = 0.001), Delta HRR1 (22.1 +/- 2.5 vs. 32.4 +/- 2.2%, p = 0.004) and Delta HRR2 (39.1 +/- 2.9 vs. 50.8 +/- 2.5%, p = 0.001) than their healthy peers. In conclusion, SLE patients presented abnormal HR response to exercise, characterized by chronotropic incompetence and delayed Delta HRR. Lupus (2011) 20, 717-720.
- 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)
article 0 Citação(ões) na Scopus Colesterol e cloroquina(2011) BORBA, Eduardo Ferreiraarticle 9 Citação(ões) na Scopus Anti-Lipoprotein Lipase Antibodies in Patients with Hypertriglyceridemia without Associated Autoimmune Disease(2011) CARVALHO, Jozelio Freire de; VIANA, Vilma Santos Trindade; BORBA NETO, Eduardo Ferreira; SANTOS, Raul Dias; BONFA, EloisaBackground: Anti-lipoprotein lipase antibodies have been described in rare cases of patients with hypertriglyceridemia. However, no systematic study evaluating these antibodies in patients with this lipid abnormality has been undertaken. Objectives: To analyze the correlation of anti-lipoprotein lipase (anti-LPL) antibodies with other laboratory findings in patients with hypertriglyceridemia but no autoimmune disease. Methods: We evaluated 44 hypertriglyceridemic patients without autoimmune disease. Clinical and laboratory evaluations included analyses of comorbidities, fasting lipid profile and anti-LPL antibodies. Results: Mean patient age was 55 +/- 10 years; 46% of the patients were female and 64% were Caucasian. The mean disease duration was 94.4 months and mean body mass index 28.7 +/- 3.6 kg/m(2); 34.0% were diabetic, 25.0% were obese, 72.7% had systemic arterial hypertension, 75% were sedentary, 15.9% were smokers, 56.8% had a family history of dyslipidemia, 45.5% had a family history of coronary insufficiency, 20.5% had acute myocardial infarction, 9.0% had undergone revascularization and 11.0% angioplasty, 79.5% were being treated with statins and 43.2% were taking fibrates. Median triglyceride levels were 254 mg/dl (range 100-3781 mg/dl), and total cholesterol level was 233 +/- 111 mg/dl. High-density lipoprotein was 42.6 +/- 15.4 mg/dl, low-density lipoprotein 110.7 +/- 42.4 mg/dl and very low-density lipoprotein 48 +/- 15 mg/dl. Anti-LPL antibodies were identified in 2 patients (4.5%), both of whom had a family history of dyslipidemia, coronary insufficiency and acute myocardial infarction; one had undergone myocardial revascularization and percutaneous transluminal coronary angioplasty, and both were using fibrates and had normal triglyceride levels. Conclusions: Our findings demonstrate a correlation between the immune response and dyslipoproteinemia in hypertriglyceridemic patients, suggesting that autoimmune disease contributes to the dyslipidemia process.- 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.
- Reduced seroprotection after pandemic H1N1 influenza adjuvant-free vaccination in patients with rheumatoid arthritis: implications for clinical practice(2011) RIBEIRO, Ana C. M.; GUEDES, Lissiane K. N.; MORAES, Julio C. B.; SAAD, Carla G. S.; AIKAWA, Nadia E.; CALICH, Ana Luisa; FRANCA, Ivan L. A.; CARVALHO, Jozelio F.; SAMPAIO-BARROS, Percival D.; GONCALVES, Celio R.; BORBA, Eduardo F.; TIMENETSKY, Maria do Carmo S.; PRECIOSO, Alexander R.; DUARTE, Alberto; BONFA, Eloisa; LAURINDO, Ieda M. M.Background Reduced response to pandemic (2009) H1N1 (pH1N1) vaccine in patients with rheumatoid arthritis (RA) was recently reported. Objectives To evaluate the contribution of age, disease activity, medication and previous antibody levels to this reduced response. Methods 340 adult RA patients and 234 healthy controls were assessed before and 21 days after adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Disease activity (DAS28), current treatment and pH1N1 antibody titres were collected. Seroprotection, seroconversion and factor increase in geometric mean titre (GMT) were calculated and adverse events registered. Results RA and controls showed similar (p> 0.05) prevaccination GMT (8.0 vs 9.3) and seroprotection (10.8% vs 11.5%). After vaccination a significant reduction (p< 0.001) was observed in all endpoints: GMT and factor increase in GMT, seroprotection and seroconversion rates. Disease activity did not preclude seroconversion or seroprotection and remained unchanged in 97.4% of patients. Methotrexate was the only disease-modifying antirheumatic drug associated with reduced responses (p= 0.001). Vaccination was well tolerated. Conclusions The data confirmed both short-term anti-pH1N1 vaccine safety and, different from most studies with seasonal influenza, reduced seroprotection in RA patients, unrelated to disease activity and to most medications (except methotrexate). Extrapolation of immune responses from one vaccine to another may therefore not be possible and specific immunisation strategies (possibly booster) may be needed.
- PPAR gamma expression is increased in systemic lupus erythematosus patients and represses CD40/CD40L signaling pathway(2011) OXER, D. S.; GODOY, L. C.; BORBA, E.; LIMA-SALGADO, T.; PASSOS, L. A.; LAURINDO, I.; KUBO, S.; BARBEIRO, D. F.; FERNANDES, D.; LAURINDO, F. R.; VELASCO, I. T.; CURI, R.; BONFA, E.; SOUZA, H. P.Systemic lupus erythematosus (SLE) is a heterogeneous disease involving several immune cell types and pro-inflammatory signals, including the one triggered by binding of CD40L to the receptor CD40. Peroxisome-proliferator activated receptor gamma (PPAR gamma) is a transcription factor with anti-inflammatory properties. Here we investigated whether CD40 and PPAR gamma could exert opposite effects in the immune response and the possible implications for SLE. Increased PPAR gamma mRNA levels were detected by real-time PCR in patients with active SLE, compared to patients with inactive SLE PPAR gamma/GAPDH mRNA = 2.21 +/- 0.49 vs. 0.57 +/- 0.14, respectively (p < 0.05) or patients with infectious diseases and healthy subjects (p < 0.05). This finding was independent of the corticosteroid therapy. We further explored these observations in human THP1 and in SLE patient-derived macrophages, where activation of CD40 by CD40L promoted augmented PPAR gamma gene transcription compared to non-stimulated cells (PPAR gamma/GAPDH mRNA = 1.14 +/- 0.38 vs. 0.14 +/- 0.01, respectively; p < 0.05). This phenomenon occurred specifically upon CD40 activation, since lipopolysaccharide treatment did not induce a similar response. In addition, increased activity of PPAR gamma was also detected after CD40 activation, since higher PPAR gamma-dependent transcription of CD36 transcription was observed. Furthermore, CD40L-stimulated transcription of CD80 gene was elevated in cells treated with PPAR gamma-specific small interfering RNA (small interfering RNA, siRNA) compared to cells treated with CD40L alone (CD80/GAPDH mRNA = 0.11 +/- 0.04 vs. 0.05 +/- 0.02, respectively; p < 0.05), suggesting a regulatory role for PPAR gamma on the CD40/CD40L pathway. Altogether, our findings outline a novel mechanism through which PPAR gamma regulates the inflammatory signal initiated by activation of CD40, with important implications for the understanding of immunological mechanisms underlying SLE and the development of new treatment strategies. Lupus (2011) 20, 575-587.