IEDA MARIA MAGALHAES LAURINDO
Projetos de Pesquisa
Unidades Organizacionais
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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- Plasma kinetics of an LDL-Like non-protein nanoemulsion and transfer of lipids to high-density Lipoprotein (HDL) in patients with rheumatoid arthritis(2015) POZZI, Fernanda S.; MARANHAO, Raul C.; GUEDES, Lissiane K.; BORBA, Eduardo F.; LAURINDO, Ieda M. M.; BONFA, Eloisa; VINAGRE, Carmen G.BACKGROUND: Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with cardiovascular risk, but with normal plasma lipids. OBJECTIVE: The aim was to investigate low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism in RA patients using radioactive nanoemulsions resembling an LDL lipid structure (LDE) as metabolic probes. METHODS: Thirty patients with RA, 16 in remission and 14 in high activity, and 30 healthy controls were studied. LDE labeled with C-14-cholesteryl ester (C-14-CE) and H-3-unesterified cholesterol (H-3-UC) was intravenously injected followed by 24 hour plasma sampling. Fractional clearance rates (FCR, h(-1)) were calculated by compartmental analysis. Lipid transfers to HDL were assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified after chemical precipitation. RESULTS: LDL cholesterol, triglycerides, unesterified cholesterol, and oxidized LDL were equal in RA and controls, and HDL cholesterol was even higher in RA. Compared with controls, apolipoprotein B was lower, apolipoprotein A1 was equal, and apolipoprotein E was higher in RA. Decay curves of LDE labels were faster in RA patients than in controls (C-14-CE: 0.072 +/- 0.066 and 0.038 +/- 0.027, P = .0115; H-3-UC: 0.066 +/- 0.042 and 0.035 +/- 0.039; P < .0044). FCRs were equal in 2 RA subgroups. Transfer of UC, triglycerides, and phospholipids to HDL was equal between RA and controls, but CE transfer was lower in RA. HDL size was smaller in RA patients than in controls (8.5 +/- 0.5 nm; 9.2 +/- 0.8 nm, P < .0001). CONCLUSION: RA patients were more efficient in removing atherogenic LDL from plasma, as indicated by higher CE and UC FCR, with in lower apolipoprotein B. This was unexpected because of the higher cardiovascular risk in RA.
- Abatacept and Reduced Immune Response to Pandemic 2009 Influenza A/H1N1 Vaccination in Patients With Rheumatoid Arthritis(2013) RIBEIRO, Ana C.; LAURINDO, Ieda M.; GUEDES, Lissiane K.; SAAD, Carla G.; MORAES, Julio C.; SILVA, Clovis A.; BONFA, EloisaObjective. To evaluate the influence of abatacept (ABA) and associated contributing factors on pandemic 2009 influenza A/H1N1 vaccine immunogenicity in rheumatoid arthritis (RA) patients. Methods. The response to a nonadjuvanted monovalent pandemic 2009 influenza A/H1N1 killed virus vaccine was analyzed in 11 RA patients using ABA (RA-ABA), most with concomitant nonbiologic disease-modifying antirheumatic drugs (DMARDS), and compared to 33 age-matched RA patients on methotrexate (MTX) and 55 healthy controls, all without previous seroprotection. Clinical and laboratory evaluations were performed before and 21 days after vaccination. Anti-influenza antibody titers were measured by hemagglutination inhibition assay. Seroprotection (antibody titers >= 1:40) and the factor increase (FI) in the geometric mean titers (GMTs) were calculated. Prevaccination lymphocyte counts and gammaglobulin levels were determined. Results. Sex distribution, disease duration, and the Disease Activity Score in 28 joints were similar in the RA groups (P > 0.05). After vaccination, seroprotection was significantly reduced in RA-ABA patients compared to RA-MTX patients (9% versus 58%; P = 0.006) and controls (69%; P <= 0.001). FI-GMT was severely reduced in RA-ABA patients compared to RA-MTX patients (1.8 [1.4-2.3] versus 8.7 [5.2-17.4]; P < 0.001) and controls (11.5 [8.0-16.7]; P <= 0.001). Lymphocyte counts were comparable in RA groups (P > 0.05), but RA-ABA patients had slightly lower gammaglobulin levels than RA-MTX patients (0.9 gm/dl [0.6-1.8] versus 1.2 gm/dl [0.8-1.7]; P = 0.03), although almost all were within the normal range values. Conclusion. The current study established that ABA, in association with traditional DMARDs, significantly reduces the humoral response to pandemic 2009 influenza A/H1N1 vaccine in RA patients. The results suggest an influence of costimulatory modulation in humoral response to this vaccine.
- LTBI screening in rheumatoid arthritis patients prior to anti-TNF treatment in an endemic area(2014) BONFIGLIOLI, K. R.; RIBEIRO, A. C. M.; MORAES, J. C. B.; SAAD, C. G. S.; SOUZA, F. H. C.; CALICH, A. L.; BONFA, E.; LAURINDO, I. M. M.SETTING: Recommendations for screening for latent tuberculous infection (LTBI) in patients eligible for antitumour necrosis factor (TNF) agents remain unclear in endemic regions. OBJECTIVE: To evaluate the long-term efficacy of LTBI screening and treatment in patients with rheumatoid arthritis (RA) receiving TNF blockers. DESIGN: A total of 202 RA patients were screened for LTBI before receiving anti-TNF treatment Using the tuberculin skin test (TST), chest X-ray (CXR) and history of exposure to tuberculosis (TB). All subjects were regularly followed at 1- to 3-month intervals. RESULTS: Eighty-five patients (42%) were treated with a single anti-TNF agent, while 117 patients (58%) changed anti-TNF agents once or twice. LTBI screening was positive in 66 patients, 44 were TST-positive, 23 had a history of TB exposure and 14 had an abnormal CXR. Exposure alone accounted for LTBI diagnosis in 14 patients with a negative TST. LTBI patients were treated with isoniazid (300 mg/day) for 6 months, and none developed TB. During follow-up, TST was repeated in 51 patients. Conversion was observed in 5; 3 were diagnosed with LTBI and 2 with active TB respectively 14 and 36 months after receiving anti-TNF treatment, suggesting new TB exposure. CONCLUSION: LTBI screening and treatment before anti-TNF treatment is effective in endemic areas and reinforces the importance of establishing contact history for diagnosing LTBI in RA patients.
conferenceObject Latent Tuberculosis Screening and Treatment in Rheumatoid Arthritis Patients Eligible for Anti-TNF Therapy in Endemic Areas: Does It Work?(2012) LAURINDO, Ieda; RIBEIRO, Ana C. M.; MORAES, Julio C. B.; SAAD, Carla G. S.; BONFIGLIOLI, Karina Rossi; SOUZA, Fernando H. C.; CALICH, Ana L. G.; WAISBERG, Mariana G.; GUEDES, Lissiane K. N.; BONFA, EloisaBackground/Purpose: Background: Current recommendations for latent tuberculosis infection (LTB) screening and treatment in patients eligible for anti-TNF agents are not well established in endemic regions. Thus, the aim of this study is to evaluate the long-term efficacy of LTB screening and treatment in RA patients under TNF blockers tight control therapeutic strategy Methods: Two hundred and two RA patients (1987 criteria) eligible for anti-TNF agents were initially screened for LTB by PPD test, chest X-ray and history of contact. Two hundred and nine patients receiving traditional DMARDs comprised the control group. Patients and controls were regularly followed at 1–3 months interval, from January 2007 to December 2011. During the study period, PPD was repeated in patients with TB clinical suspicion or due to extended ( 12 months) interruption/re-start of biologic treatment. Results: 202 patients were treated with anti-TNF blockers, 85(42%) with one agent and 117(58%) with two or more: 181 received infliximab, 93 adalimumab and 75 etanercept. LTB screening (PPD and/or history of contact and/or X-ray) was positive in 69(34%) patients. In 65%(45 patients) PPD was positive, 36%(n 25) had history of contact and 21%(n 15) with X-ray alterations. Of note, in the 24 LTB patients with negative PPD, contact history accounted for 75% and X-ray for 37% of the positive screened cases. LTB treatment with isoniazid during 6 months was administered to all positive screened patients and none developed TB during follow-up. Regarding the 133 remaining screening negative patients none had TB during the first twelve months of anti-TNF therapy. PPD test was repeated in only 53 patients (26%) due to interruption/re-start of biologic treatment (51cases) or clinical TB suspicion (2 cases). PPD turned out to be positive in five patients: three that received LTB treatment and the two patients with clinical TB suspicion, both diagnosed as active TB (after 14 and 36 months of anti-TNF treatment) and properly treated with standard TB treatment. In those RA patients under traditional DMARDs, three cases (1.5%) of active TB were observed. Thus, the frequency of TB in RA patients during five years of observation was similar in patients under biological and traditional DMARDs (1% vs. 1.5%, p 0.68), although higher than the expected for the area (60/100,000/ per year). Conclusion: The present study provided evidence that the recommended screening and treatment protocol for LTB in patients under anti-TNF treatment was also efficient in endemic areas, with a special attention to contact history in those with negative PPD. Active TB diagnosis during anti-TNF treatment seems not to be related to screening failure, reinforcing the importance of constant clinical surveillance.- 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.
- LTBI screening in rheumatoid arthritis patients prior to anti-TNF treatment in an endemic area (vol 18, pg 905, 2014)(2014) BONFIGLIOLI, K. R.; RIBEIRO, A. C. M.; MORAES, J. C. B.; SAAD, C. G. S.; SOUZA, F. H. C.; CALICH, A. L.; BONFA, E.; LAURINDO, I. M. M.
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.- TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients(2012) FRANCA, Ivan Leonardo Avelino; RIBEIRO, Ana Cristina Medeiros; AIKAWA, Nadia Emi; SAAD, Carla Goncalves Schain; MORAES, Julio Cesar Bertacine; GOLDSTEIN-SCHAINBERG, Claudia; LAURINDO, Ieda Maria Magalhaes; PRECIOSO, Alexander Roberto; ISHIDA, Maria Akiko; SARTORI, Ana Marli Christovam; SILVA, Clovis Artur; BONFA, EloisaMethods. One hundred and twenty patients (RA, n = 41; AS, n = 57; PsA, n = 22) on anti-TNF agents (monoclonal, n = 94; soluble receptor, n = 26) were compared with 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection, seroconversion (SC), geometric mean titre, factor increase in geometric mean titre and adverse events were evaluated 21 days after vaccination. Results. After immunization, SC rates (58.2% vs 74.3%, P = 0.017) were significantly lower in SpA patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared with healthy controls (P = 0.067). SpA patients receiving mAbs (infliximab/adalimumab) had a significantly lower SC rate compared with healthy controls (51.6% vs 74.3%, P = 0.002) or those on DMARDs (51.6% vs 74.7%, P = 0.005), whereas no difference was observed for patients on etanercept (86.7% vs 74.3%, P = 0.091). Further analysis of non-seroconverting and seroconverting SpA patients revealed that the former group had a higher mean age (P = 0.003), a higher frequency of anti-TNF (P = 0.031) and mAbs (P = 0.001) and a lower frequency of MTX (P = 0.028). In multivariate logistic regression, only older age (P = 0.015) and mAb treatment (P = 0.023) remained significant factors for non-SC in SpA patients. Conclusion. This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in SpA patients using mAbs. Trial Registration: ClinicalTrials.gov, ext-link-type=""uri"" xlink:href=""www.clinicaltrials.gov"" xmlns:xlink=""http://www.w3.org/1999/xlink"">www.clinicaltrials.gov, NCT01151644.