CARLA GONCALVES SCHAHIN SAAD
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/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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- 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.
- Systemic and localized infection by Candida species in patients with rheumatic diseases receiving anti-TNF therapy(2016) AIKAWA, Nadia E.; ROSA, Daniela T. A.; NEGRO, Gilda M. B. Del; MORAES, Julio C. B.; RIBEIRO, Ana C. M.; SAAD, Carla Goncalves; SILVA, Clovis A.; BONFA, EloisaObjective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA), 47 with ankylosing spondylitis (AS), 36 with juvenile idiopathic arthritis (JIA), 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 +/- 16 years, with 68 (35%) male and mean disease duration of 15 +/- 10 years. Sixty-four (33%) patients were receiving adalimumab, 59 (30%) etanercept and 71 (36%) infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5%) patient had localized fungal infection (vaginal candidiasis). None of the patients included had systemic candidiasis with positive blood cultures for fungi or IDCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use. (C) 2015 Elsevier Editora Ltda.
- HLA-B27 positivity in a large miscegenated population of 5,389,143 healthy blood marrow donors in Brazil(2023) RESENDE, Gustavo Gomes; SAAD, Carla Goncalves Schahin; OLIVEIRA, Danielli Cristina Muniz de; BUENO FILHO, Julio Silvio de Sousa; SAMPAIO-BARROS, Percival Degrava; PINHEIRO, Marcelo de MedeirosBackgroundThe prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil.AimTo estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database.MethodsThis is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence.ResultsFrom 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population.ConclusionsOur findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.
- Testicular Sertoli cell function in ankylosing spondylitis(2013) ALMEIDA, Breno Pires; SAAD, Carla Goncalves Schahin; SOUZA, Fernando Henrique Carlos; MORAES, Julio Cesar Bertacini; NUKUMIZU, Lucia Akemi; VIANA, Vilma Santos Trindade; BONFA, Eloisa; SILVA, Clovis ArturTo assess the testicular Sertoli cell function according to inhibin B levels in ankylosing spondylitis (AS) patients and the possible effect of anti-TNF therapy on this hormone production, 20 consecutive AS patients and 24 healthy controls were evaluated. At study entry, AS patients were not receiving sulfasalazine/methotrexate and never have used biological/cytotoxic agents. They were assessed by serum inhibin B levels, hormone profile, urological examination, testicular ultrasound, seminal parameters, and clinical features. Ten of these patients received anti-TNF treatment and they were reevaluated for Sertoli function and disease parameters at 6 months. Four of them agreed to repeat sperm analysis. At study entry, the median of inhibin B (68 vs. 112.9 pg/mL, p = 0.111), follicle-stimulating hormone levels (3.45 vs. 3.65 IU/L, p = 0.795), and the other hormones was comparable in AS patients and controls (p > 0.05). Sperm analysis was similar in AS patients and controls (p > 0.05) with one AS patient presenting borderline low inhibin B levels. Further analysis at 6 months of the 10 patients referred for anti-TNF therapy, including one with borderline inhibin B, revealed that median inhibin B levels remained stable (116.5 vs. 126.5 pg/mL, p = 0.431) with a significant improvement in C-reactive protein (27.8 vs. 2.27 mg/L, p = 0.039). Sperm motility and concentration were preserved in the four patients who repeated this analysis after TNF blockage. In conclusion, this was the first study to report, using a specific marker, a normal testicular Sertoli cell function in AS patients with mild to moderate disease activity.
- Interaction of TNFi and conventional synthetic DMARD in SARS-CoV-2 vaccine response in axial spondyloarthritis and psoriatic arthritis(2023) SAAD, Carla G. S.; SILVA, Matheus S. R.; SAMPAIO-BARROS, Percival D.; MORAES, Julio C. B.; SCHAINBERG, Claudia G.; GONCALVES, Celio R.; SHIMABUCO, Andrea Y.; AIKAWA, Nadia E.; YUKI, Emily F. N.; PASOTO, Sandra G.; KUPA, Leonard V. K.; AOYAMA, Renato K.; ARAUJO, Carlo S. R.; SILVA, Clovis A.; MEDEIROS-RIBEIRO, Ana C.; BONFA, EloisaObjectives: To evaluate humoral responses to three doses of the inactivated SARS-CoV-2 vaccine (CoronaVac) in patients with spondyloarthritis (SpA) and the effect of therapy, compared with a control group (CG).Methods: Prospective cohort of axial SpA/psoriatic arthritis patients and age/sex-balanced CG from the CoronavRheum phase 4 trial (NCT04754698). CoronaVac was given in two doses (28-days interval) with a booster at day 210. Blood samples were collected in the days 0/28 (D28)/69 (D69) and 240 (D240) to evaluate anti-SARS-CoV-2 IgG seropositivity (SP) and neutralising antibodies (NAb).Results: One hundred and ninety-four SpA patients were enrolled and 183 patients were age/sex-balanced with 183 CG. At D69, SpA patients showed a high SP (80.2% vs. 95.7%, P < 0.001) and moderate NAb positivity (61.6% vs. 82.7%, P < 0.001), but lower than CG. In patients, older age prednisone (P < 0.001), methotrexate (MTX) (P < 0.001) and TNF inhibitors (TNFi) (P < 0.001) were independently associated with lower SP, while Caucasian ethnicity (P < 0.05) and prednisone (P < 0.01) were associated with diminished NAb. In contrast, sulfasalazine (SSZ) use was associated with NAb presence (P < 0.05). In monotherapy, only TNFi was also associated with absence of SP (P < 0.05). Further comparison with CG revealed that TNFi and/or MTX negatively impacted SP/NAb (P < 0.05). In contrast, patients under SSZ monotherapy achieved 100% SP (P > 0.999) and 83.3% NAb positivity (P > 0.999). SSZ + TNFi combination resulted in a similar response than CG [SP (P = 0.153) and NAb (P = 0.715)]. After third dose (D69-D240), a major increment occurred for SP (81.3% to 93.1%, P < 0.001) and NAb (63.2% to 86.1%, P < 0.001), but still lower than CG (P < 0.05), and only TNFi impaired both SP (P = 0.016)/NAb (P = 0.002).Conclusions: We provided novel data demonstrating that TNFi attenuates immunogenicity in SpA patients while SSZ has a positive impact on vaccine antibody production. We also confirmed that MTX in combination with TNFi had a major negative impact in vaccine humoral response (CoronavRheum clinicaltrials.gov #NCT04754698).(c) 2022 Socie acute accent te acute accent franc , aise de rhumatologie.
- Factors associated with ASDAS remission in a long-term study of ankylosing spondylitis patients under tumor necrosis factor inhibitors(2018) SHIMABUCO, Andrea Y.; GONCALVES, Celio R.; MORAES, Julio C. B.; WAISBERG, Mariana G.; RIBEIRO, Ana Cristina de M.; SAMPAIO-BARROS, Percival D.; GOLDENSTEIN-SCHAINBERG, Claudia; BONFA, Eloisa; SAAD, Carla G. S.Objective: To determine the clinical and demographic factors associated with disease remission and drug survival in patients with ankylosing spondylitis (AS) on TNF inhibitors. Methods: Data from a longitudinal electronic database of AS patients under anti-TNF therapy between June/2004 and August/2013. Demographic, clinical parameters, disease activity by ASDAS remission (< 1.3) and inactive/low (< 2.1) were analyzed to characterize reasons for drug survival and switching of anti-TNF. Results: Among 117 AS patients, 69 (59%) were prescribed only one anti-TNF, 48 (41%) switched to a second anti-TNF and 13 (11%) to a third anti-TNF. Considering ASDAS-CRP < 1.3, 31 (39%) patients were inactive at the end of the study. Non-switchers (P = 0.04), younger age (P = 0.004), non-smoking (P = 0.016), shorter disease duration (P = 0.047), more frequent use of SSZ (P = 0.037) and lower BASDAI (P = 0.027), BASMI (P = 0.034) and BASFI (P = 0.003) at baseline were associated with remission. In the multivariate analysis younger age (P = 0.016) and lower BASDAI (P = 0.032) remained as remission predictors. Conclusion: This study supports that ASDAS-CRP remission is an achievable goal not only for non-switchers but also for second anti-TNF, particularly in patients with younger age and lower BASDAI at baseline. Co-medication and non-smoker status seems to have a beneficial effect in anti-TNF response in this population.
- Brazilian recommendations for the use of nonsteroidal anti-inflammatory drugs in patients with axial spondyloarthritis(2021) LAGE, Ricardo da Cruz; MARQUES, Claudia Diniz Lopes; OLIVEIRA, Thauana Luiza; RESENDE, Gustavo Gomes; KOHEM, Charles Lubianca; SAAD, Carla Goncalves; XIMENES, Antonio Carlos; GONCALVES, Celio Roberto; BIANCHI, Washington Alves; MEIRELLES, Eduardo de Souza; KEISERMAN, Mauro Waldemar; CHIEREGHIN, Adriano; CAMPANHOLO, Cristiano Barbosa; LYRIO, Andre Marun; SCHAINBERG, Claudia Goldenstein; PIERUCCETTI, Lenise Brandao; YAZBEK, Michel Alexandre; PALOMINOS, Penelope Esther; GONCALVES, Rafaela Silva Guimaraes; ASSAD, Rodrigo Luppino; BONFIGLIOLI, Rubens; LIMA, Sonia Maria Alvarenga Anti Loduca; CARNEIRO, Sueli; AZEVEDO, Valderilio Feijo; ALBUQUERQUE, Cleandro Pires; BERNARDO, Wanderley Marques; SAMPAIO-BARROS, Percival Degrava; PINHEIRO, Marcelo de MedeirosSpondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. Over some decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been the basis for the pharmacological treatment of patients with axial spondyloarthritis (axSpA). However, the emergence of the immunobiologic agents brought up the discussion about the role of NSAIDs in the management of these patients. The objective of this guideline is to provide recommendations for the use of NSAIDs for the treatment of axSpA. A panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis of randomized clinical trials for 15 predefined questions. The Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations were used, and at least 70% agreement of the voting panel was needed. Fourteen recommendations for the use of NSAIDs in the treatment of patients with axSpA were elaborated. The purpose of these recommendations is to support clinicians' decision making, without taking out his/her autonomy when prescribing for an individual patient.
- NT-proBNP levels may be influenced by inflammation in active ankylosing spondylitis receiving TNF blockers: a pilot study(2013) MORAES, Julio C. B.; RIBEIRO, Ana C. M.; SAAD, Carla G. S.; LIANZA, Alessandro C.; SILVA, Clovis A.; BONFA, EloisaN-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong marker of cardiovascular disease with recent evidence that inflammation may also influence its levels; discrimination of this confounding variable is of particular interest in rheumatic diseases. Therefore, we evaluated NT-proBNP in ankylosing spondylitis (AS) patients pre- and post-TNF blocker to determine the possible association between NT-proBNP levels and inflammatory parameters. Forty-five consecutive AS patients without previous/current cardiovascular disease or systolic myocardial dysfunction, who were eligible to anti-TNF therapy, were prospectively enrolled. All patients received TNF blockers and they were evaluated for circulating NT-proBNP levels, clinical and laboratory parameters of disease activity, traditional cardiovascular risk factors, and conventional and tissue Doppler imaging echocardiography at baseline (BL) and 6 months after (6M) treatment. At BL, all patients had active AS, NT-proBNP levels had a median of 36 (20-72) pg/mL and 11 % were high in spite of no systolic alteration. Multiple linear regression analysis revealed that this peptide, at BL, was independently correlated with erythrocyte sedimentation rate (ESR) (p < 0.001), age (p = 0.01), and pulse pressure (p = 0.01). After 6M, all disease parameters improved and NT-proBNP levels were significantly reduced [24 (16-47) pg/mL, p = 0.037] compared to BL. Changes in NT-proBNP were positively correlated with ESR changes (r = 0.41, p = 0.006). Cardiovascular risk factors remained stable during follow-up. In conclusion, our data suggest that elevations of NT-proBNP should be interpreted with caution in active AS patients with no other evidence of cardiovascular disease. The short-term reduction of NT-proBNP levels in these patients receiving anti-TNF therapy appears to reflect an improvement in inflammatory status.
- Assessing bone impairment in ankylosing spondylitis (AS) using the trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT)(2019) CAPARBO, Valeria F.; FURLAM, Pedro; SAAD, Carla G. S.; ALVARENGA, Jackeline C.; AUBRY-ROZIER, Berengere; HANS, Didier; BRUM-FERNANDES, Artur J. de; PEREIRA, Rosa M. R.Objectives: To compare bone quality using the trabecular bone score (TBS) and bone microarchitecture in the distal tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) in ankylosing spondylitis (AS) patients and healthy controls (HC). Methods: Areal bone mineral density (aBMD) and TBS (TBS iNsight software) were evaluated using DXA (Hologic, QDR 4500); while volumetric bone mineral density (vBMD) and bone microarchitecture were analyzed in the distal tibia using HR-pQCT (Scanco) in 73 male patients with AS and 52 age-matched HC. Results: AS patients were a mean 41.6 +/- 7.9 years old and had a mean disease duration of 16.4 +/- 8.6 y, with a mean mSASSS 25.6 +/- 16.4. No difference was observed in lumbar spine aBMD in AS patients and HC (p = 0.112), but total hip BMD (p = 0.011) and TBS (p < 0.001) were lower in AS patients. In the distal tibia, reduced trabecular volumetric density [Tb.vBMD (p < 0.006)] and structural alterations - trabecular thickness (Tb.Th), p = 0.044 and trabecular separation (Tb.Sp), p = 0.039 - were observed in AS patients relative to controls. Further analysis comparing TBS < 1.310 and TBS >= 1.310 in AS patients revealed a higher mean body mass index [BMI] (p = 0.010), lower tibia cortical vBMD [Ct.vBMD] (p = 0.007), lower tibia cortical thickness [Ct.Th] : (p = 0.048) in the former group. On logistic regression analysis, BMI (OR = 1.27; 95%IC = 1.08-1.50, p = 0.005), (VF 4.65; 1.13-19.1, p = 0.033) and tibial Ct.vBMD (0.98; 0.97-1.00, p = 0.007) were associated with a lower TBS ( < 1.310). Conclusions: The present study demonstrates that TBS and HR-pQCT imaging are important technologies evaluating bone impairment in AS patients. Moreover, in these patients vertebral fractures were associated with lower TBS.
- Monocytes from male patients with ankylosing spondylitis display decreased osteoclastogenesis and decreased RANKL/OPG ratio(2018) CAPARBO, V. F.; SAAD, C. G. S.; MORAES, J. C.; BRUM-FERNANDES, A. J. de; PEREIRA, R. M. R.aSummaryThe present study investigates the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) in male patients with ankylosing spondylitis (AS). We demonstrated that monocytes from these patients display a lower capacity to generate osteoclasts compared to cells from healthy controls, and osteoclastogenesis was negatively correlated with disease duration.IntroductionAnkylosing spondylitis (AS) is a disease characterized by new bone growth that leads to syndesmophyte formation but AS patients frequently present with low bone mineral density/fractures. Osteoclastogenesis in AS patients is poorly studied and controversial. The aim of this study is to determine if the osteoclastogenic capacity of PBMCs is different in AS patients compared to controls and the relationship between osteoclastogenesis and clinical/laboratory parameters.MethodsPBMCs from 85 male AS patients and 59 controls were tested for CD16+ cells and induced to differentiate into osteoclasts over 3weeks in vitro. Serum levels of RANKL, osteoprotegerin (OPG), C-terminal telopeptide of type I collagen (CTX), and amino-terminal pro-peptide of type I collagen (P1NP) were also evaluated.ResultsPBMCs from AS patients had fewer CD16+ cells and produced fewer osteoclasts compared to controls. Apoptosis occurred less frequently in osteoclasts obtained from AS patients than in osteoclasts from the controls. A lower RANKL/OPG and CTX/P1NP were observed in AS patients compared to controls. AS patients taking NSAIDs presented no difference regarding the number of OCs produced and the percentage of CD16+ cells compared to controls. However, patients taking TNF inhibitors (TNFi) presented lower OC numbers than controls. A negative correlation was demonstrated between the number of osteoclasts generated from PBMCs of AS patients and disease duration.ConclusionMonocytes from male AS patients display a lower capacity to generate osteoclasts in vitro compared to cells from controls. Osteoclastogenesis was negatively correlated with disease duration. This finding supports the idea that osteoclasts play a role in the physiopathology of bone disease in AS patients.