Navegando por Palavras-chave "Autoantibodies"

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    Antibodies to citrullinated peptides are not associated with the rate of joint destruction in patients with a well-established diagnosis of rheumatoid arthritis
    (Associação Brasileira de Divulgação Científica, 2008-03-01) Nieto-Colonia, Alberto Max [UNIFESP]; Santos, Wilton Silva dos [UNIFESP]; Keusseyan, Silene Peres [UNIFESP]; Caldana, Wanda [UNIFESP]; Fernandes, Artur da Rocha Correa [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Escola Superior de Ciências da Saúde Faculdade de Medicina
    Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis (RA) and represent a significant risk factor for undifferentiated polyarthritis. This prognostic ability may be related to the very diagnostic performance of these autoantibodies, since RA is a more erosive disease than other forms of arthritis. The present study evaluated an association of antibodies to citrullinated peptides and the rate of joint destruction in patients with a well-established diagnosis of RA. Seventy-one patients with RA were evaluated in 1994 and again in 2002 (functional class, joint count, Health Assessment Questionnaire score, hands X-ray). Autoantibodies (rheumatoid factor (RF), anti-perinuclear factor, anti-cyclic citrullinated peptide (CCP) antibodies) and Sharp's index were analyzed blindly. Delta Sharp was calculated as the difference in Sharp's index obtained in 1994 and 2002. During the follow-up the Health Assessment Questionnaire score increased from 0.91 ± 0.74 to 1.39 ± 0.72 (P < 0.001). Similarly, the number of swollen joints increased from 4.6 ± 5.71 to 6.4 ± 4.1 (P = 0.002). The frequency of autoantibodies and anti-CCP titer remained stable; however, serum RF concentration increased from 202.8 ± 357.6 to 416.6 ± 636.5 IU/mL (P = 0.003). Sharp's index increased from 56.7 ± 62.1 to 92.4 ± 80.9 (P < 0.001). No correlation was observed between Delta Sharp and the presence of RF, anti-perinuclear factor, and anti-CCP antibodies at baseline. Antibodies to citrullinated epitopes are specific and early markers for the diagnosis of RA but do not seem to be associated with the rate of joint destruction in patients with a well-established diagnosis of RA.
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    Association of autoantibodies anti-OxLDL and markers of inflammation with stage of HIV infection
    (Elsevier B.V., 2013-09-30) Orellana, Ronald Vargas; Fonseca, Henrique Andrade Rodrigues da [UNIFESP]; Monteiro, Andrea Moreira; Ortega, Karem Lopez; Gallottini, Marina Helena; Gidlund, Magnus; Pobocik, Andrea Mantesso; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
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    AutoAbSC.Org - Autoantibody standardization committee in 2006
    (Elsevier B.V., 2007-09-01) Chan, Edward K. L.; Fritzler, Marvin J.; Wiik, Allan; Andrade, Luis E. C.; Reeves, Westley H.; Tincani, Angela; Meroni, Pier Luigi; IUIS WHO AF CDC comm Standardi; Univ Florida; Univ Calgary; State Serum Inst; Universidade Federal de São Paulo (UNIFESP); Osped Civile; Univ Milan
    The Autoantibody Standardization Committee was established in the early 1980s based on the recognized needs for reference human autoimmune sera that were critical for academic, clinical, and industrial laboratories. To date, 14 reference reagents are available without charge from the Biological Reference Reagents distribution center at the Centers for Disease Control and Prevention. A web site has been developed under AutoAbSC.Org to communicate to the wider stakeholder community and to facilitate ongoing activities in continuing the mission in autoantibody standardization. (c) 2007 Elsevier B.V. All rights reserved.
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    Autoantibodies before, during and after administration of recombinant interferon-alpha for chronic viral hepatitis
    (Instituto de Medicina Tropical, 1995-10-01) Lopes, Edmundo P.a. [UNIFESP]; Silva, Antonio Eduardo Benedito [UNIFESP]; Sette Junior, Hoel; Guimarães, Rubens X. [UNIFESP]; Ferraz, Maria Lucia Cardoso Gomes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Hospital Oswaldo Cruz
    This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha) therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.
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    Autoantibodies to 60 kDa SS-A/Ro yield a specific nuclear myriad discrete fine speckled immunofluorescence pattern
    (Elsevier B.V., 2013-04-01) Dellavance, Alessandra; Alvarenga, Rossana Rassi [UNIFESP]; Rodrigues, Silvia Helena [UNIFESP]; Barbosa, Silvia Helena; Pinto Camilo, Amandia Cristina; Okamoto Shiguedomi, Herika Santiago; Rodrigues, Silvia Sanchez; Silva, Cristiane Gallindo; Coelho Andrade, Luis Eduardo [UNIFESP]; Fleury Med & Hlth Labs; Universidade Federal de São Paulo (UNIFESP)
    Objectives: To report on a novel immunofluorescence pattern specifically associated with antibodies to SS-A/Ro.Methods: A novel immunofluorescence pattern, herein designated SS-A/Ro pattern, was characterized as myriad discrete fine speckles throughout the nucleus. Eighty-six sequential samples presenting the SS-A/Ro pattern and 64 samples presenting non-SS-A/Ro nuclear fine speckled pattern at the ANA-HEp-2 routine were screened for SS-A/Ro reactivity. Conversely, 48 samples with known reactivity to 60 kDa SS-A/Ro, 13 samples with exclusive reactivity to 52 kDa SS-A/Ro, and 48 SS-A/Ro-negative samples were analyzed for the ANA-HEp-2 pattern.Results: Eighty-five of the 86 samples (98.8%) presenting the SS-A/Ro pattern and 15 of the 64 (23.4%) samples with non-SS-A/Ro fine speckled pattern reacted with 60 kDa SS-A/Ro. Conversely, 44 (91.6%) of 48 samples with known reactivity to 60 kDa SS-A/Ro presented the SS-A/Ro pattern and four (8.4%) presented non-SS-A/Ro fine speckled pattern. None of the 48 anti-SS-A/Ro-negative samples and none of anti-52 kDa SS-A/Ro-positive samples yielded the SS-A/Ro pattern. This immunofluorescence pattern was observed in different commercial HEp-2 cell slides and in homemade HEp-2 cell slides.Conclusions: the SS-A/Ro pattern belongs to the group of immunofluorescence patterns that hold strong association with the respective autoantibody specificities, such as those associated with CENP-F and NuMA-1. the identification of the SS-A/Ro pattern at the ANA-HEp-2 screening routine shall lead to specific tests for the identification of anti-SS-A/Ro antibodies. (C) 2013 Elsevier B.V. All rights reserved.
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    Avaliação clínica e sorológica de pacientes com uveíte anterior aguda segundo a presença do alelo HLA-B27
    (Universidade Federal de São Paulo (UNIFESP), 1997) Trevisani, Virginia Fernandes Moça [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]
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    Caracterização de autoanticorpos associados ao padrão de imunofluorescência “Rods & Rings” em pacientes infectados com o vírus da Hepatite C
    (Universidade Federal de São Paulo (UNIFESP), 2011-07-27) Keppeke, Gerson Dierley [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introdução: Pacientes com Hepatite C frequentemente tendem a produzir autoanticorpos. No teste fator antinúcleo em células HEp-2 (ANA-HEp-20), esses autoanticorpos geram diversos padrões de imunofluorescência, sendo o nuclear pontilhado fino o mais frequente deles. Recentemente, tem sido descrito um novo padrão de ANA-HEp-2 em pacientes com HCV, denominado padrão Rods e Rings (R&R), caracterizado por anéis e bastões. Objetivos: Avaliar as características clínicas, virológicas e padrão de resposta terapêutica dos pacientes que apresentam autoanticorpos que geram o padrão R&R, bem como proceder a uma avaliação preliminar dos aspectos celulares e moleculares desse novo sistema de autoantígenos. Métodos: Amostras de soro coletadas de 1998 até 2008 de 597 pacientes foram submetidas ao teste de ANA-HEp-2 em lâminas Euroimmun ou INOVA e classificados como R&R positivos quando apresentaram fluorescência sob forma de bastões de 3 a 10μm de comprimento e anéis de 2 a 5μm de diâmetro no citoplasma das células HEp-2. Entre os pacientes testados, 342 tinham HCV e 200 tinham outras doenças hepáticas crônicas ou autoimunes reumáticas, além de 55 pacientes co-infectados com HCV+HIV. As informações clínicas, virológicas e terapêuticas foram coletadas de bancos de dados atrelados às amostras de soro dos pacientes. Células HEp-2, 3T3 e MH22A foram cultivadas normalmente e/ou submetidas à tratamentos in vitro (tripsina e ribavirina) e com dois métodos alternativos de fixação, para estudo das estruturas do R&R por imunofluorescência indireta simples ou com técnicas de dupla-marcação com amostras R&R-positivas e anticorpos antitubulina-alfa e anti-CTP-sintase. Resultados: Dos 342 pacientes com HCV, 51 (15%) apresentaram o padrão R&R, enquanto que dos 200 pacientes com outras doenças hepáticas ou autoimunes, apenas um apresentou o padrão R&R (p<0.0001). Dos pacientes com HCV, 174 eram tratados e 168 não tratados. Dos 174 tratados, 49 (28%) apresentaram o padrão R&R contra apenas dois (1%) dos não tratados (p<0.0001). De 134 tratados e com informação adequada sobre a medicação utilizada, 108 tomavam interferon-α e ribavirina e 23 tomavam apenas interferon-α. Quarenta e um (38%) dos 103 que tomavam interferon-α e ribavirina apresentaram o padrão R&R contra nenhum (0%) dos 23 que tomavam apenas interferon-α (p= 0.0001). Quanto aos outros padrões de ANA-HEp-2, dos 23 pacientes que tomavam apenas interferon-α, 12 (52%) foram positivos enquanto apenas 27 (25%) dos que tomavam interferon-α e ribavirina foram positivos (p= 0.010). 9% dos pacientes co-infectados com HCV+HIV apresentaram o padrão R&R. Não encontramos relação entre a presença do padrão R&R e o genótipo do vírus, a carga viral e os dados demográficos dos pacientes com HCV. A porcentagem de respondedores ao tratamento foi ligeiramente menor nos pacientes que apresentaram o R&R, porem sem atingir nível de significância estatística (p=0,150). Lâminas ANA-HEp-2 de algumas marcas comerciais que não Euroimmun e INOVA e aquelas elaboradas no próprio laboratório não apresentaram as estruturas do R&R. Quando tratadas in vitro com ribavirina ou tripsina, as células HEp-2 ou 3T3 e MH22A de camundongo cultivadas expressaram vários anéis e bastões reconhecidos pelas amostras de soro R&R-positivas. Não observamos colocalização das estruturas R&R com microtúbulos e observamos fraca colocalização dos anéis e bastões com CTP-sintase. Conclusões: Autoanticorpos associados ao padrão R&R ocorreram em íntima associação ao uso de interferon-α e ribavirina em pacientes com hepatite HCV, independentemente de serem portadores do HIV. Não houve associação às características demográficas dos pacientes, ao perfil de resposta terapêutica, ao genótipo do HCV ou à carga viral. As estruturas em anéis e bastões associadas ao padrão R&R não ocorrem nas condições normais avaliadas, podendo ser induzidas in vitro pela exposição à ribavirina ou à tripsina. Há algum grau de conservação filogenética dos autoantígenos associados ao padrão R&R. Evidências preliminares indicam a presença da enzima CTP-sintase nas estruturas em anéis e bastões reconhecidas pelos autoanticorpos humanos.
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    Caracterização vascular periférica de pacientes portadores de glaucoma primário de ângulo aberto
    (Universidade Federal de São Paulo (UNIFESP), 2020-12-18) Muller, Elise Vivan Taniguchi [UNIFESP]; Paranhos Junior, Augusto [UNIFESP]; Universidade Federal de São Paulo
    Purpose: To evaluate peripheral microvascular characteristics of primary open-angle glaucoma (POAG) patients and healthy controls, along with endothelin-1 serum concentration and autoantibodies measurements. Patients and Methods: Subjects underwent a visual field test (Humphrey Visual Field Analyzer, Carl Zeiss, Dublin, USA), swept source optical coherence tomography (SS-OCT) (Deep Range Imaging OCT Triton, Topcon, Tokyo, Japan), nailfold capillaroscopy (NFC) (Stereo Microscope SZ40, Olympus, Tokyo, Japan), laser Doppler imaging (LDI) (Moor LDI-VR, Moor Instruments, Axminster, United Kingdom) and venous blood collection. Ophthalmic tests evaluated the presence and the stage of POAG and confirmed the absence of any abnormality among controls. NFC evaluated the presence and the number of microhemorrhages, tortuous capillaries, branched capillaries, dilated capillaries, mega-capillaries and bizarre capillaries, besides the number of capillary loops/mm and the deletion score; LDI measured fingertip blood flow (FBF) in four different timepoints and blood samples were evaluated for determination of serum endothelin-1 concentrations along with serum auto-antibodies measurements. Results: Sixty-eight subjects (43 patients with POAG and 25 healthy controls) were enrolled in the study. 65.1% of POAG patients presented with hemorrhages in the nailfold capillaroscopy versus 25.0% of healthy controls (p=0.003, chi-Square). There was a significant difference in the mean FBF at baseline in POAG patients vs. controls (293.6 ± 100.2 vs. 388.8 ± 52.0 perfusion units [PU]), respectively, p<0.001, mixed models), together with a significant difference in the mean FBF 10 and 20 minutes after cold stimulus in POAG patients in comparison to controls (p<0.001 for all comparisons, mixed models). However, nor the analysis of endothelin-1 concentrations (1.7 ± 1.4 vs. 1.6 ± 1.5 pg/ml, p=0.71, t-test) or the autoantibodies measurements (p>0.05 for all, chi-square) showed any difference between the groups. There was a positive correlation between basal FBF of LDI and retina nerve fiber layer (RNFL) measurements from SS-OCT (r=0.441, p=0.001, Pearson’s correlation coefficient), as well as between basal FBF and the mean deviation index of visual field (r=0.272, p=0.03, Pearson’s correlation coefficient). Conclusions: POAG patients presented significant peripheral microvascular abnormalities compared to healthy controls. This study supports the vascular theory associated to POAG.
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    The challenge of identification of autoantibodies specific to systemic autoimmune rheumatic diseases in high throughput operation: Proposal of reliable and feasible strategies
    (Elsevier B.V., 2014-11-01) Costa Pereira, Kaline Medeiros [UNIFESP]; Dellavance, Alessandra [UNIFESP]; Coelho Andrade, Luis Eduardo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fleury Med & Hlth Labs
    Background: Autoantibodies to extractable nuclear antigens (ENA) are good biomarkers for systemic autoimmune rheumatic diseases (SARD), but no one assay for the detection of these antibodies provides satisfactory sensitivity and positive predictive value (PPV). Here we evaluate current assays and propose novel strategies to detect anti-ENA antibodies.Methods: Diagnostic performance of double immunodiffusion (DID) and several enzyme immunoassays (EIA) for the detection of anti-ENA autoantibodies was determined using samples from 144 patients with a previous clinical diagnosis of SARD and 121 non-autoimmune individuals. A 2-step assay combining EIA and DID was developed and tested on 16,458 serum samples.Results: EIA was more sensitive than DID for all anti-ENA antibodies, but yielded lower PPV (mean = 66%) than DID (mean = 96%) and a higher percentage of unexpected positive results. ROC-curve guided cut-off adjustments improved PPV for most EIA kits. Using the 2-step assay, over 80% of the samples were screened out by the first step (EIA), with results available within 24 h, leaving only about 20% to be confirmed by DID. 2.9% of the 16,485 samples were found to be positive.Conclusions: A 2-step assay combining the speed and potential for automation of EIA with the high specificity and PPV of DID allows efficient and reliable detection of anti-ENA antibodies. Alternatively, improved PPV can be achieved by adjusting cut-off values for EIA assay results. (C) 2014 Elsevier B.V. All rights reserved.
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    Como interpretar e valorizar adequadamente o teste de anticorpos antinúcleo
    (Sociedade Brasileira de Patologia ClínicaSociedade Brasileira de PatologiaSociedade Brasileira de Citopatologia, 2007-06-01) Dellavance, Alessandra [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fleury Medicina Diagnóstica Setor de Imunologia
    The tradicional fluorescent antinuclear antibody test (ANA) has required constant update efforts from personel involved in performing and interpreting its results. The methodological advances have brought up a considerable improvement in the test s sensitivity and, consequentely, a decrease in its specificity. This has resulted in an increasing number of positive tests in apparently healthy subjects. However, there are some peculiar features associated with the auto-antibodies in patients with autoimmune diseases that are not present in those observed in healthy subjects. The objective of the present review is to bring an approach on the most important points to be considered in the analysis and evalution of an ANA test that might help in the identification of patients with autoimmune disease. Title and immunofluorescence pattern are discussed as important parameters and they are important in the evaluation of ANA and in the reflex demand for further tests for specific autoantibodies. The basic concepts of the National Consensus on Standardization of ANA-HEp-2 Report are posted. Finally, we explore the possible meanings of a positive ANA test in a patient without objective evidence of autoimmune disease.
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    Comparative study of ophthalmological and serological manifestations and the therapeutic response of patients with isolated scleritis and scleritis associated with systemic diseases
    (Conselho Brasileiro de Oftalmologia, 2011-12-01) Sousa, Jacqueline Martins de [UNIFESP]; Trevisani, Virgínia Fernandes Moça [UNIFESP]; Modolo, Rodrigo Pilon [UNIFESP]; Gabriel, Luís Alexandre Rassi [UNIFESP]; Vieira, Luis Antonio [UNIFESP]; Freitas, Denise de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de Santo Amaro
    INTRODUCTION: Scleritis is a rare, progressive and serious disease, the signs of which are inflammation and edema of episcleral and scleral tissues and is greatly associated with systemic rheumatoid diseases. PURPOSE: To perform a prospective and comparative study between ophthalmologic manifestations, serologic findings and therapeutic response of patients with isolated scleritis and scleritis associated with systemic rheumatoid disease. METHODS: Thirty-two outpatients with non-infectious scleritis were studied, from March 2006 to March 2008. The treatment was corticoid eye drops associated with anti-inflammatory agents, followed by systemic corticoids and immunosuppressive drugs if necessary, was considered successful after six months without scleritis recurrence. RESULTS: Fourteen of 32 patients had scleritis associated with systemic rheumatoid disease, of which nine had rheumatoid arthritis, two systemic lupus erythematosus, one Crohn's disease, one Behçet's disease and one gout. There were no difference in relation to involvement and ocular complications, there was predominance of nodular anterior scleritis and scleral thinning was the most frequent complication. The scleritis associated with systemic rheumatoid disease group had 64.3% of autoantibodies, versus 27.8% among those with isolated scleritis and this difference was statistically significant. In the isolated scleritis group 16.7% used anti-inflammatory, 33.3% corticosteroids, 27.8% corticosteroids with one immunosuppressive drug, 5.5% two immunosuppressive drugs, 16.7% corticosteroids with two immunosuppressive drugs and 33.3% pulse of immunosuppressive drugs, there was remission in 88.9%. In the scleritis associated with systemic rheumatoid disease group 7.1% used anti-inflammatory, 7.1% corticosteroids, 50% corticosteroids with one immunosuppressive drug, 7.1% two immunosuppressive drugs and 22.2% pulse of immunosuppressive drugs, 100% had treatment success. CONCLUSION: Prevalence of unilateral nodular scleritis was noted in both groups and higher rates of all the parameters tested were noted in the scleritis associated with systemic rheumatoid disease group. There were no differences between the groups with respect to the use of immunosuppressive drugs and therapeutic response, which was fully satisfactory in the scleritis associated with systemic rheumatoid disease group and satisfactory in the isolated scleritis group.
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    Detecção de anticorpos anti-rods and rings (anti-RR) em portadores de Hepatite C crônica submetidos a tratamento
    (Universidade Federal de São Paulo (UNIFESP), 2017-09-28) Nunes, Eunice Jadriana Soares [UNIFESP]; Ferraz, Maria Lucia Cardoso Gomes [UNIFESP]; http://lattes.cnpq.br/1870810357457710; http://lattes.cnpq.br/4555655578786530; Universidade Federal de São Paulo (UNIFESP)
    Background: Patients with chronic hepatitis C often have serum autoantibodies. In 2015, the international consensus for autoantibody research recognized a new pattern of autoantibodies against HEp-2 cells antigens found mostly in patients treated for hepatitis C, which shows rods and rings (RR) structures. The main antigenic target is the enzyme inosine monophosphate dehydrogenase (IMPDH), involved in the synthesis of new guanosine nucleotides that can aggregate in the presence of inhibitory drugs. The objective of this study was to evaluate the occurrence of anti-RR antibodies in patients submitted to one or two treatments with interferon (IFN) and/or ribavirin (RBV) and to correlate positive results to epidemiological, clinical, virological, histological and therapeutic features. Casuistic and Method: Patients with chronic hepatitis C followed at the Hepatitis Division of the Gastroenterology Discipline at UNIFESP were enrolled. Data were retrospectively collected from medical records. Anti-RR was determined by immunofluorescence technique in HEp-2 cells. Results: Of the 112 patients included, none had anti-RR reactivity before first treatment. At the end of the first treatment, anti-RR reactivity was found in 28.5% of the patients (n = 32/112) and all had received double therapy with IFN+RBV (p = 0.003). Due to therapeutic failure, 63 patients underwent a second treatment, of which 12 (19%) already had anti-RR reactivity. From 51 patients who entered the second treatment without anti-RR reactivity, 30/51 (58.8%) developed anti-RR positivity. Positivity increased significantly from the first to the second treatment (p <0.001). By comparing the groups with and without anti-RR reactivity, a higher frequency of anti-RR was observed in the patients who used a full dose of ribavirin (p < 0.001). On the other hand, anti- RR was less frequent in patients with parenteral transmission (p = 0.007) and comorbidities (hemodialysis, renal transplantation and HIV coinfection; p = 0.005). Conclusion: Anti-RR reactivity is induced by dual treatment (interferon + ribavirin) and positivity increases with successive treatments and higher exposure to ribavirin. The absence of a relationship with clinical, virological, histological and response to therapy characteristics suggests that, like other autoantibodies, it is an epiphenomenon associated with the treatment
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    Diabetes mellitus in a young Amazon Indian child
    (Associação Paulista de Medicina - APM, 2005-03-01) Gabbay, Monica Andrade Lima [UNIFESP]; Bussad, Edson [UNIFESP]; Persoli, Ligia [UNIFESP]; Volpini, Walkiria [UNIFESP]; Dib, Sergio Atala [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    CONTEXT: Although type 2 diabetes has been described among American Indian children, no case of type 1 diabetes has been reported in the literature. CASE REPORT: We report the first case of diabetes in a South American Indian child from the tropical rainforest, who was positive for IA2 autoantibodies and genetic markers of susceptibility to type 1 diabetes, but also demonstrated residual beta cell function four years after diagnosis.
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    Doença de addison de etiologia auto-imune
    (Sociedade Brasileira de Endocrinologia e Metabologia, 1998-12-01) Silva, Regina do Carmo [UNIFESP]; Kater, Claudio Elias [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Autoimmune Addison's disease is a rare and potentially, fatal endocrinopathy, that can occur either isolated or as part of the types I and II polyglandular autoimmune syndromes (PAS). Adrenocortical autoantibodies are considered sensitive immunological markers of the destructive autoimmune process, and can identify individuals in the pre-clinical stage of the disease. The steroidogenic enzyme 21-hydroxylase (P450c21) represents the major adrenal autoantigen, although other P450 cytochromes (17a-hydroxylase and side chain cleavage) can also trigger an autoimmune response, mainly in the PAS type I and in Addison's disease with associated premature ovarian failure. The role of P45021 autoantibodies in the pathogenesis of the adrenal failure is not yet well established, and the same happens with the anti-ACTH receptor antibodies.
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    Estudo da expressão dos auto-antígenos SS-A/Ro (polipeptídeos 52kda e 60kda) e SS-B/La (polipeptídeo 48kda) e de seus RNAs mensageiros em glândulas salivares menores de pacientes com síndrome de Sjögren
    (Universidade Federal de São Paulo (UNIFESP), 2006-12-31) Silveira, Karin Spat Albino Barcellos [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Purpose: The strong association between primary Sjögren syndrome (pSS) and autoantibodies to SS-A/Ro (52kDa and 60kDa) and SS-B/La may be indicative of a possible role for these autoantigens in the pathophysiology of the disease. The present study aimed to analyze protein and mRNA expression of SS-A/Ro and SS-B/La antigens in a preferential tissue target of pSS, i.e., minor salivary glands (MSGs). Methods: SS-A/Ro (60kDa & 52kDa) and SS-B/La protein expression was studied by immunohistochemistry in MSG samples of 26 pSS patients and 16 control subjects. Analysis was carried out by two independent blinded observers according to the topography and intensity (semiquantitative score) of the staining. Total RNA extracted from MSG samples of 10 pSS patients and 7 control subjects was submitted to reverse transcription and quantified by Real Time PCR with primers specific to SS-A/Ro (60kDa & 52kDa) and SS-B/La cDNA. Samples were normalized by ß-actin and GAPDH mRNA expression. Relative mRNA expression (2-ΔΔCT) was compared between pSS patients and control subjects. Results: In general the semiquantitative protein expression for the three autoantigens did not differ among pSS patients and control subjects, and was more prominent in the cytoplasm as compared to the nucleus in all cell types. However, SS-B/La protein had higher expression in the cytoplasm of ductal cells than in the cytoplasm of mucous acinar cells in pSS patients (p=0.013), while no significant difference was detected in the control group (p=0.704). SS-A/Ro 60kDa protein had higher expression in the cytoplasm of ductal cells than in the cytoplasm of serous acinar cells of pSS patients (p=0.006) but the same was not observed for controls (p=0.156). SS-A/Ro 52kDa protein topographic expression pattern was the same in patients and controls. SS-B/La mRNA expression was higher in samples from pSS patients (5.326±5.107) than in controls (0.856±1.255) (p=0.0311). The same was true for SS-A/Ro 60kDa mRNA expression (6.866±7.868 vs 1.045±1.329; p=0.0330). On the other hand, SS-A/Ro 52kDa mRNA expression showed a modest trend for higher expression in samples from pSS patients but the difference did not reach statistical significance (5.616±4.885 vs 2.648±4.223; p=0.0879). Samples with the highest histological inflammation score at MSG showed decreased expression of SS-A/Ro 60kDa, SS-A/Ro 52kDa and SS-B/La mRNAs. Conclusions: The increased SS-A/Ro 60kDa and SS-B/La mRNA expression in MSGs of pSS patients as well as the differential SS-A/Ro 60kDa and SS-B/La protein expression in ductal cells of MSGs in pSS patients suggest that these antigens are probably involved in triggering and maintaining the tissue-specific autoimmune response in pSS MSGs. The observed differential expression may contribute to the antigen-driven immune response and local autoantibody production in pSS.
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    Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis
    (Springer, 2013-06-01) Dellavance, Alessandra [UNIFESP]; Cancado, Eduardo Luiz Rachid; Abrantes-Lemos, Clarice Pires; Harriz, Michelle [UNIFESP]; Marvulle, Valdecir [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fleury Med & Hlth Labs; Universidade de São Paulo (USP)
    To compare autoantibody features in patients with primary biliary cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but no clinical or biochemical evidence of disease.A total of 212 AMA-positive serum samples were classified into four groups: PBC (definite PBC, n = 93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and ELISA [antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100, and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG was determined by 8 M urea-modified ELISA.High-titer IIF-AMA was more frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and 19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013, respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36-4.29) and PBC/AID samples (3.89; 3.15-4.63) than in BN (2.43; 1.92-2.94) and BN/AID samples (2.52; 1.54-3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in PBC (mean 64.5 %; 95 % CI 57.5-71.5 %) and PBC/AID samples (66.1 %; 54.4-77.8 %) than in BN samples (39.2 %; 30.9-37.5 %) (p < 0.001). PBC and PBC/AID recognized more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere) than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were independently associated with established PBC: high-avidity anti-PDC-E2 (OR 4.121; 95 % CI 2.118-8.019); high-titer IIF-AMA (OR 4.890; 2.319-10.314); antibodies to three or more antigenic cell domains (OR 9.414; 1.924-46.060).The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals.
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    II Consenso Brasileiro de Fator Antinuclear em Células HEp-2: Definitions for standardization of autoantibody testing against the nucleus (ANA HEp-2), nucleolus, cytoplasm and mitotic apparatus, as wel as its clinical associations
    (Sociedade Brasileira de Reumatologia, 2003-06-01) Dellavance, Alessandra [UNIFESP]; Gabriel Júnior, Alexandre [UNIFESP]; Cintra, Alice Friedenberg de Ulhôa; Ximenes, Antônio Carlos; Nuccitelli, Barbara; Taliberti, Ben Hur; Moreira, Caio; Von Mühlen, Carlos Alberto; Bichara, Carlos David Araújo; Santos, Cláudio Henrique Ramos dos; Yano, Cristiane Martinez; Mangueira, Cristóvão Luis Pitangueiras; Carvalho, Darlene Gonçalves; Bonfá, Eloisa Silva Dutra de Oliveira; Doi, Elvira M.; Guimarães, Fabiana Nunes de Carvalho; Araújo, Flávia Ikeda e; Mundim, Hugo Mendonça; Rego, Jozelia; Vieira, Lisiane Ericonio dos Anjos; Poli, Luciana; Andrade, Luiz Eduardo Coelho [UNIFESP]; Callado, Maria Roseli; Mesquita, Mauro Meira; Sugiyama, Mitiko; Slhessarenko, Natasha; Silva, Nilzio Antônio da; Carballo, Orlando Gabriel; Leser, Paulo Guilherme [UNIFESP]; Francescantonio, Paulo Luiz Carvalho; Jarach, Renata; Xavier, Ricardo Machado; Levy, Roger Abramino; Neves, Suzane Pretti Figueiredo; Cruvinel, Wilson de Melo [UNIFESP]; Santos, Wilton Silva dos [UNIFESP]; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Bio-Rad Laboratório Brasil; Hospital Geral de Goiânia; Biomédica; Universidade Federal de Uberlândia; UFMG HC; PUCRS HC; New Life Produtos Hospitalares; Universidade Católica de Goiás; Patologista Clínica; Frischmann Aisengart Unidad Inmunología; Universidade Católica de Goiás Laboratório de Auto-Imunidade; Exame Medicina Laboratorial; FMUFG HC Laboratório de Imuno-Reumatologia e HLA; Lab. Santa Luzia; Medivax/Bion; HSPE/SP; Universidade Católica de Goiás Laboratório da Área de Saúde; Farmacêutica-Bioquímica; Univ. Fed. Mato Grosso; FMUFG Serviço de Reumatologia; Hospital Durand Unidad Inmunología; Laboratório Clínico; UFRGS HCPA Serviço de Reumatologia; UERJ FCM; UFMG FM; Hospital Universitário de Brasília Laboratório de Reumatologia
    OBJECTIVE: The Second Brazilian Consensus on Antinuclear Antibodies (ANA) in HEp-2 Cells approved and extended the decision trees developed during the First Brazilian Consensus in order to also offer information about mixed patterns of fluorescence. METHODS: Since this test elicits reactions not only to nuclear autoimmune antigens but also to different cell compartments, new denominations for the test were approved. Results and CONCLUSIONS: These new denominations encompass variations on the autoantibody testing against the nucleus (ANA HEp-2), nucleolus, cytoplasm, and mitotic apparatus issue. Furthermore, major clinical associations were described for each immunofluorescent pattern, facilitating the interpretation of laboratory results in the clinical practice.
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    III Consenso Brasileiro para Pesquisa de Autoanticorpos em Células HEp-2: perspectiva histórica, controle de qualidade e associações clínicas
    (Sociedade Brasileira de Patologia ClínicaSociedade Brasileira de PatologiaSociedade Brasileira de Citopatologia, 2009-06-01) Francescantonio, Paulo Luiz Carvalho; Andrade, Luiz Eduardo Coelho [UNIFESP]; Cruvinel, Wilson de Melo [UNIFESP]; Araújo, Flávia Ikeda e; Dellavance, Alessandra [UNIFESP]; Gabriel Júnior, Alexandre [UNIFESP]; Nuccitelli, Barbara; Taliberti, Ben Hur; Von Mühlen, Carlos Alberto; Bichara, Carlos David Araújo; Santos, Cláudio Henrique Ramos dos; Bueno, Cleonice; Yano, Cristiane Martinez; Mangueira, Cristóvão Luis Pitangueiras; Carvalho, Darlene Gonçalves; Cardoso, Elizângela; Bonfá, Eloisa Silva Dutra de Oliveira; Rassi, Gustavo Gabriel; Mundim, Hugo Mendonça; Bendet, Izidro; Rego, Jozelia; Vieira, Lisiane Maria Enriconi dos Anjos; Barbosa, Maria Ordália Ferro; Sugiyama, Mitiko; Santiago, Mittermayer Barreto; Slhessarenko, Natasha; Silva, Nilzio Antônio da; Jarach, Renata; Suda, Roberto; Levy, Roger Abramino; Sampaio, Silvia Oliveira; Neves, Suzane Pretti Figueiredo; Santos, Wilton Silva dos [UNIFESP]; Nóbrega, Yanna Karla de Medeiros; UCG; Universidade Federal de São Paulo (UNIFESP); Fleury Medicina e Saúde setor de Imunologia; UCG Departamento de Biomedicina Laboratório de Apoio Didático; Centro Imuno-Reumatológico de São Paulo AFIP-Medicina Laboratorial; Padrão Laboratório Clínico; Universidade Federal de Uberlândia; UFU Hospital das Clínicas serviço de reumatologia; Pontifícia Universidade do Rio Grande do Sul Faculdade de Medicina; Metanalysis Centro de Diagnósticos Médicos; Universidade Federal do Pará; Laboratório Amaral Costa; Centro de Educação Técnica do Estado do Pará; NewLife Comércio de Produtos Laboratoriais; Universidade de São Paulo (USP); Hospital Israelita Albert Einstein Departamento de Patologia Clínica; Instituto Hermes Pardini; Biometrix Diagnóstica; Laboratório Atalaia; Sérgio Franco Medicina Diagnóstica setor de Imunoensaios; UCG Faculdade de Medicina Hospital das Clínicas; Universidade do Sul de Santa Catarina; Universidade do Vale do Itajaí; Laboratório Médico Santa Luzia; Hospital e Maternidade e Jardim América Laboratórios Saúde; Hemagen Diagnósticos; Universidade Federal da Bahia; Fundação Bahiana para Desenvolvimento das Ciências; Hospital Santa Izabel serviço de reumatologia; Universidade Federal de Mato Grosso; FMUCG; Alka; Universidade do Estado do Rio de Janeiro; Hospital Pró-cardíaco Centro de Autoimunidades; Diagnósticos da América SA; Laboratório Diagnósticos da América SA setor de Imunologia; Universidade Federal de Minas Gerais Faculdade de Medicina; UFMG Hospital das Clínicas Serviço de Medicina Laboratorial; Hospital Universitário de Brasília Laboratório de Reumatologia; União Educacional do Planalto Central; Centro Universitário Euro-Americano; Imunotech Sistemas Diagnósticos Importação e Exportação
    OBJECTIVE: The Third Brazilian Consensus for Autoantibodies Screening in HEp-2 Cells (ANA) had as purpose the evaluation of difficulties in the accomplishment of the 2nd Consensus recommendations that took place in the year of 2002, the discussion of strategies for quality control of the assay and the discussion of an update of the clinical associations of the several immunofluorescent patterns. METHODS: Several ANA experts from university centers and private laboratories in different areas in Brazil joined the workshop in Goiânia on 2007 April 13 and 14 with the purpose of discussing and approving the recommendations for standardization, interpretation and use of the test by physicians. Commercial representatives of different ANA slide brands were also invited as listeners to the workshop. RESULTS AND CONCLUSION: The 3rd ANA Consensus emphasized the need for quality control in indirect immunofluorescent assays since there is a considerable heterogeneity of available microscopes and reagents. It also promoted adaptations in the previously approved terminology used to classify the different patterns and finally updated the clinical associations of the several patterns with the purpose of providing guidance for interpretation of the assay by clinical pathologists and assistant physicians.
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    Inflammatory environment and immune responses to oxidized LDL are linked to systolic and diastolic blood pressure levels in hypertensive subjects
    (Elsevier B.V., 2012-05-17) Fonseca, Henrique Andrade Rodrigues da [UNIFESP]; Fonseca, Francisco Antonio Helfenstein [UNIFESP]; Monteiro, Andrea Moreira; Farias, Nelson Carvalho; Bianco, Henrique Tria [UNIFESP]; Brandão, Sergio Augusto Bueno [UNIFESP]; Póvoa, Rui Manoel dos Santos [UNIFESP]; Gidlund, Magnus; Izar, Maria Cristina de Oliveira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Natl Inst Complex Fluids
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    International consensus on ana patterns (icap): the bumpy road towards a consensus on reporting ana results
    (Springer-verlag italia srl, 2016) Damoiseaux, Jan; von Muhlen, Carlos A.; Garcia-De La Torre, Ignacio; Gabriel Carballo, Orlando; Cruvinel, Wilson de Melo; Carvalho Francescantonio, Paulo Luiz; Fritzler, Marvin J.; Herold, Manfred; Mimori, Tsuneyo; Satoh, Minoru; Andrade, Luis E. C. [UNIFESP]; Chan, Edward K. L.; Conrad, Karsten
    The International Consensus on ANA Patterns (ICAP) was initiated as a workshop aiming to thoroughly discuss and achieve consensus regarding the morphological patterns observed in the indirect immunofluorescence assay on HEp-2 cells. One of the topics discussed at the second ICAP workshop, and addressed in this paper, was the harmonization of reporting ANA test results. This discussion centered on the issue if cytoplasmic and mitotic patterns should be reported as positive or negative. This report outlines the issues that impact on two major different reporting methods. Although it was appreciated by all participants that cytoplasmic and mitotic patterns are clinically relevant, implications for existing diagnostic/classification criteria for ANA-associated diseases in particular hampered a final consensus on this topic. Evidently, a more concerted action of all relevant stake-holders is required. Future ICAP workshops may help to facilitate this action.