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Background/Objective: Myasthenia Gravis (MG) is an autoimmune disorder characterized by pathogenic autoantibodies (AAbs) targeting nicotinic acetylcholine receptors (AChR), disrupting neuromuscular communication. RadioImmunoPrecipitation Assay (RIPA) is recommended to detect AChR AAbs, but its complexity and radioactive requirements limit widespread use. We compare non-RIPA anti-AChR immunoassays, including Cell-Based Assay (CBA) and two ELISA kits, against the gold standard RIPA. Methods/Results: 145 samples were included with medical indication for anti-AChR testing. By the RIPA method, 63 were negative (RIPA-Neg <â0.02 nmol/L), 18 were classified as Borderline (≥0.02 -1 nmol/L), and 64 were positive (RIPA-Posâ>â1 nmol/L). The competitive ELISA showed poor agreement with RIPA (Kappaâ=â0.216). The indirect ELISA demonstrated substantial agreement with RIPA (Kappaâ=â0.652), with â¼76% sensitivity and â¼94% specificity for MG diagnostic. The CBA, where fixed cells expressing clustered AChR were used as substrate, exhibited almost perfect agreement with RIPA (Kappaâ=â0.984), yielding â¼98% sensitivity and 96% specificity for MG. In addition, a semiquantitative analysis showed a strong correlation between CBA titration, indirect ELISA, and RIPA levels (râ=â0.793 and râ=â0.789, respectively). Conclusions: The CBA displayed excellent analytical performance for MG diagnostic when compared to RIPA, making it a potential replacement for RIPA in clinical laboratories. Some solid-phase assays (such as the indirect ELISA applied here), as well as CBA titration, offer reliable options to estimate anti-AChR AAb levels after confirming positivity by the CBA.â¥.
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Autoanticorpos , Ensaio de Imunoadsorção Enzimática , Miastenia Gravis , Ensaio de Radioimunoprecipitação , Humanos , Ensaio de Imunoadsorção Enzimática/métodos , Miastenia Gravis/imunologia , Miastenia Gravis/diagnóstico , Sensibilidade e Especificidade , Receptores Colinérgicos/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adulto JovemRESUMO
Personalized medicine (PM) aims individualized approach to prevention, diagnosis, and treatment. Precision Medicine applies the paradigm of PM by defining groups of individuals with akin characteristics. Often the two terms have been used interchangeably. The quest for PM has been advancing for centuries as traditional nosology classification defines groups of clinical conditions with relatively similar prognoses and treatment options. However, any individual is characterized by a unique set of multiple characteristics and therefore the achievement of PM implies the determination of myriad demographic, epidemiological, clinical, laboratory, and imaging parameters. The accelerated identification of numerous biological variables associated with diverse health conditions contributes to the fulfillment of one of the pre-requisites for PM. The advent of multiplex analytical platforms contributes to the determination of thousands of biological parameters using minute amounts of serum or other biological matrixes. Finally, big data analysis and machine learning contribute to the processing and integration of the multiplexed data at the individual level, allowing for the personalized definition of susceptibility, diagnosis, prognosis, prevention, and treatment. Autoantibodies are traditional biomarkers for autoimmune diseases and can contribute to PM in many aspects, including identification of individuals at risk, early diagnosis, disease sub-phenotyping, definition of prognosis, and treatment, as well as monitoring disease activity. Herein we address how autoantibodies can promote PM in autoimmune diseases using the examples of systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, Sjögren syndrome, systemic sclerosis, idiopathic inflammatory myopathies, autoimmune hepatitis, primary biliary cholangitis, and autoimmune neurologic diseases.
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Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Autoanticorpos , Humanos , Medicina de Precisão , Síndrome de Sjogren/complicaçõesRESUMO
The classification and diagnosis of systemic autoimmune diseases are frequently based on a collection of criteria composed of clinical, laboratory, imaging, and pathology elements that are strongly associated with the respective disease. Autoantibodies are a distinctive hallmark and have a prominent position in the classification criteria of many autoimmune diseases. The indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA), historically known as the antinuclear antibody test, is a method capable of detecting a wide spectrum of autoantibodies. A positive HEp-2 IFA test is part of the classification criteria for systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA), as well as the diagnostic criteria for autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). A positive HEp-2 IFA test can appear as different morphological patterns that are indicative of the most probable autoantibody specificities in the sample. Only some of the HEp-2 IFA patterns are associated with the specific autoantibodies relevant to SLE, JIA, AIH, and PBC, whereas some other patterns occur mainly in non-related conditions and even in apparently healthy individuals. This paper provides a critical review on the subject and proposes that the classification and diagnostic criteria for SLE, JIA, AIH, and PBC could be improved by a modification on the HEp-2 IFA (ANA) criterion in that the staining patterns accepted for each of these diseases should be restricted according to the respective relevant autoantibody specificities.
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ABSTRACT Introduction: The detection of autoantibodies in HEp-2 cells represents a relevant tool for the diagnosis of autoimmune diseases, especially rheumatic autoimmune diseases. As a result of the methodological advances, the technique gradually increased the sensitivity, as well as the need for standardization. Objective: To evaluate the implementation of the Brazilian Consensus recommendations for autoantibody determination in HEp-2 cells. Methods: A structured form in a virtual platform was filled in by experts in clinical laboratories that carry out the methodology across the country. The questionnaire addressed the adoption of the Brazilian Consensus guidelines, detailing the technical aspects, quality control, the strategy for reading slides and the release of reports. Results: The study included 53 laboratories responsible for more than 300,000 antinuclear antibody (ANA) tests/month; more than half (58.5%) reported fully adopting the recommendations of the Brazilian Consensus. The majority (83.1%) used the 1:80 for screening dilution, and 75.5% of laboratories, perform education and quality control programs. Only 39.6% reported using more than one kit brand to perform the test, and 32.1% did not report observing all phases of the cell cycle during slide reading. The study also detected some heterogeneity among participants in the identification of patterns. Conclusion: The results confirm the adoption of the Brazilian Consensus recommendations by most of participating laboratories, although with variable extent. There is need for improvement in some aspects, especially those related to the quality control.
RESUMO Introdução: A pesquisa de autoanticorpos em células HEp-2 representa uma relevante ferramenta no auxílio diagnóstico de doenças autoimunes, especialmente as reumáticas. Em virtude dos avanços metodológicos, a técnica aumentou gradativamente a sensibilidade, bem como a necessidade de padronização. Objetivo: Avaliar a implantação das recomendações dos consensos brasileiros de pesquisa de autoanticorpos em células HEp-2. Métodos: Preenchimento de formulário em plataforma virtual direcionada aos laboratórios clínicos que realizam a metodologia. Os participantes responderam a um questionário sobre a adoção das diretrizes dos consensos brasileiros, detalhando os aspectos técnicos, o controle de qualidade, a leitura de lâminas e a emissão de laudos. Resultados: Participaram do estudo 53 laboratórios responsáveis por mais de 300 mil testes de fator antinuclear (FAN)/mês; mais da metade (58,5%) informou adotar integralmente as recomendações dos consensos. A maioria (83,1%) utiliza a diluição 1:80 para triagem, e 75,5% dos laboratórios, programas de educação e controle de qualidade. Apenas 39,6% utilizam mais de uma marca de kit para a realização do teste, e 32,1% não relataram observar todas as fases do ciclo celular na leitura da lâmina. O estudo detectou ainda discreta heterogeneidade entre participantes na identificação de padrões. Conclusão: Os resultados evidenciam a adoção das recomendações dos consensos de forma absoluta pela maioria dos laboratórios participantes, bem como a necessidade de aperfeiçoamento em alguns aspectos relevantes para a qualidade do ensaio.
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Capilares/efeitos dos fármacos , Dermatomiosite/tratamento farmacológico , Imunossupressores/uso terapêutico , Capilares/diagnóstico por imagem , Capilares/patologia , Pré-Escolar , Dermatomiosite/diagnóstico por imagem , Dermatomiosite/patologia , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/farmacologia , Angioscopia Microscópica , Unhas/irrigação sanguíneaAssuntos
Humanos , Feminino , Pré-Escolar , Capilares/efeitos dos fármacos , Dermatomiosite/tratamento farmacológico , Imunossupressores/uso terapêutico , Capilares/patologia , Capilares/diagnóstico por imagem , Angioscopia Microscópica , Dermatomiosite/patologia , Dermatomiosite/diagnóstico por imagem , Quimioterapia Combinada , Imunossupressores/farmacologia , Unhas/irrigação sanguíneaRESUMO
The objective of this study was to demonstrate the presence of mycobacterial nucleic acid sequences in peripheral blood and arteries from patients with Takayasu arteritis (TA). Polymerase chain reaction was performed to detect mycobacterial DNA from three different nucleic acid sequences including the insertion sequence (IS) 6110, the 65-kDa heat shock protein gene (HSP65), and the 16S ribosomal RNA (rRNA) gene in peripheral blood from 32 TA patients and in arterial specimens from 10 TA patients. Twenty-eight HIV-negative patients with pulmonary tuberculosis prior to therapy were tested for IS6110 in peripheral blood as positive controls, and 24 blood donors were evaluated as healthy controls (HC). All TA patients were negative for the insertion sequence IS6110 and for HSP65 and 16S rRNA genes in blood samples and in arterial specimens. IS6110 sequence was found in peripheral blood from 22 (78.5 %) patients with pulmonary tuberculosis but not in HC. In conclusion, the strategy of mycobacterial-specific nucleic acid amplification in the peripheral blood and arterial specimens of TA patients was unable to lend support to the association between TA and tuberculosis long suggested in the literature.
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Artérias/microbiologia , DNA Bacteriano/sangue , Arterite de Takayasu/microbiologia , Adolescente , Adulto , Proteínas de Bactérias/genética , Estudos de Casos e Controles , Chaperonina 60/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Arterite de Takayasu/sangue , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/epidemiologiaRESUMO
Chronic inflammation associated with hepatitis C virus (HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α (IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies (ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings (RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings (anti-RR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.
Assuntos
Anticorpos Antinucleares/imunologia , Antivirais/efeitos adversos , Autoimunidade/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , IMP Desidrogenase/imunologia , Interferon-alfa/efeitos adversos , Ribavirina/efeitos adversos , Quimioterapia Combinada , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/imunologia , Humanos , IMP Desidrogenase/antagonistas & inibidores , IMP Desidrogenase/química , Imunidade Humoral/efeitos dos fármacos , Conformação Proteica , Tolerância a Antígenos Próprios/efeitos dos fármacos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To test the hypothesis that classical phagocytic functions are constitutively stimulated in patients with Behçet's disease (BD). METHODS: Four study groups were analysed: active BD (aBD; n=30), inactive BD (iBD; n=31); septic patients (SP; n=25); healthy controls (HC; n=30). Microbicide activity against Streptococcus pneumoniae, Streptococcus sanguinis and Candida albicans was determined by means of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and absorbance read by ELISA. Flow cytometry analysis evaluated phagocytosis (zymosan particles and microrganisms) and oxidative burst by dihidrorhodamine oxidation before and after stimulation with phorbol myristate acetate (PMA). The supernatant of PBMC cultures under TLR or microbial stimuli and of neutrophil cultures under PMA, LPS or microbial stimuli were used for determination of cytokine production by ELISA. RESULTS: We found no significant differences between the BD patient groups and control groups with regard to oxidative burst, phagocytic activity, microbicide activity or cytokine production. However, the cells from patients with severe BD (based on clinical manifestation) exhibit significantly higher oxidative burst activity, both before and after PMA stimulation, compared to cells from patients with mild BD. Furthermore, we found significant correlations between the BD patients' scores on the simplified Behçet's Disease Current Activity Form adapted for Portuguese (BR-BDCAFs) and Streptococcus sanguinis-stimulated production of IL23 by PBMC and IL8 by neutrophils, and between BR-BDCAFs score and constitutive production of TNF-α, IFNγ, IL6 and IL23 by PBMC. CONCLUSIONS: Patients with severe active BD do exhibit phagocytic dysfunction and some evidence of constitutive activation regarding oxidative burst and cytokine production.
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Síndrome de Behçet/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Ativação de Neutrófilo , Neutrófilos/metabolismo , Fagocitose , Explosão Respiratória , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Candida albicans/imunologia , Estudos de Casos e Controles , Células Cultivadas , Citocinas/imunologia , Feminino , Humanos , Mediadores da Inflamação/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/microbiologia , Fagocitose/efeitos dos fármacos , Fenótipo , Explosão Respiratória/efeitos dos fármacos , Índice de Gravidade de Doença , Streptococcus pneumoniae/imunologia , Streptococcus sanguis/imunologia , Acetato de Tetradecanoilforbol/farmacologia , Adulto JovemRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals.
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BACKGROUND: A novel pattern in the indirect immunofluorescence antinuclear antibody assay on HEp-2 cells (IIF-HEp-2) characterized by cytoplasmic rods and rings (RR) was reported in HCV patients, but stringent disease specificity studies and longitudinal analysis are lacking. We investigated the clinical significance of anti-RR in an HCV cohort with up to a 12-month treatment follow up. METHODOLOGY/RESULTS: 597 patients (342 HCV, 55 HCV/HIV, 200 non-HCV) were screened and titered for anti-RR. Serial samples were available from 78 of 176 treated and 27 of 166 untreated patients. Anti-RR was detected in 14.1% of 342 HCV patients, 9.1% of 55 HCV/HIV, 3.4% of 29 Hepatitis B, and none of 171 non-HCV (p<0.0001; HCV versus non-HCV). Anti-RR was present in 38% of 108 patients receiving interferon-α/ribavirin, but none in 26 receiving either interferon-α or ribavirin, or 166 untreated patients (p<0.0001). Other IIF-HEp-2 patterns were more frequently associated with interferon-α treatment alone (52.2%) as compared to interferon-α/ribavirin (25%), ribavirin alone (33.3%), and no therapy (26.5%). Anti-RR frequency was not associated with sex, age, ethnicity, HCV genotype or viral load. Anti-RR occurred only after initiation of treatment, beginning as early as 1 month (6%), but by the sixth month >47% tested positive for anti-RR. The anti-RR titer generally increased with sustained treatment and remained high in 53% of patients. After treatment, anti-RR titer was negative in 41%. Non-responders to HCV therapy were 77% in anti-RR-positive versus 64% in anti-RR-negative patients. Response to treatment was not associated with anti-RR titer or the dynamics of anti-RR reactivity during and after treatment. CONCLUSIONS: The exquisite association of anti-RR reactivity with combined interferon-α/ribavirin therapy in HCV patients represents a unique model for drug-induced autoantibody generation in humans as demonstrated by the fact that a significant fraction of patients who have anti-RR during therapy becomes anti-RR-negative after completion of therapy.
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Antivirais/uso terapêutico , Autoanticorpos/metabolismo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To analyze cytokine gene expression in keratinocytes from patients with systemic lupus erythematosus (SLE). INTRODUCTION: Keratinocytes represent 95% of epidermal cells and can secrete several cytokines. METHODS: Keratinocytes were obtained by laser microdissection from 21 patients with SLE (10 discoid and 11 acute lesions) at involved and uninvolved sites. All patients were receiving a low/moderate prednisone dose and 18 were receiving chloroquine diphosphate. IL-2, IL-5, TNF-α and IFN-γ gene expression was evaluated by real-time PCR and expressed as the ratio (R) to a pool of skin samples from 12 healthy volunteers. RESULTS: Heterogeneity in cytokine gene expression was found among patients with SLE. Eighteen of 38 valid SLE samples (47%) presented overexpression (R>1) of at least one cytokine. Lesional skin samples tended to show higher cytokine expression than samples from uninvolved skin (p = 0.06). IL-5 and IFN-γ were the most commonly overexpressed cytokines. Samples with cytokine overexpression corresponded to more extensive and severe lesions. Prednisone dose did not differ between samples without cytokine overexpression (15.71±3.45 mg/day) and those with overexpressed cytokines (12.68±5.41 mg/day) (p = 0.216). Samples from all patients not receiving diphosphate chloroquine had at least one overexpressed cytokine. CONCLUSIONS: The heterogeneous keratinocyte cytokine gene expression reflects the complex immunological and inflammatory background in SLE. Patients with severe/extensive skin lesions showed a higher frequency of cytokine gene overexpression. Increased IFN-γ and IL-5 expression suggests that Th1 and Th2 cells are involved in SLE skin inflammation. The possibility that prednisone and antimalarial drugs may have contributed to low cytokine gene expression in some samples cannot be ruled out.
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Citocinas/genética , Expressão Gênica/genética , Queratinócitos/metabolismo , Lúpus Eritematoso Sistêmico/genética , Dermatopatias/genética , Adulto , Citocinas/metabolismo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Dermatopatias/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To analyze cytokine gene expression in keratinocytes from patients with systemic lupus erythematosus (SLE). INTRODUCTION: Keratinocytes represent 95 percent of epidermal cells and can secrete several cytokines. METHODS: Keratinocytes were obtained by laser microdissection from 21 patients with SLE (10 discoid and 11 acute lesions) at involved and uninvolved sites. All patients were receiving a low/moderate prednisone dose and 18 were receiving chloroquine diphosphate. IL-2, IL-5, TNF-α and IFN-γ gene expression was evaluated by real-time PCR and expressed as the ratio (R) to a pool of skin samples from 12 healthy volunteers. RESULTS: Heterogeneity in cytokine gene expression was found among patients with SLE. Eighteen of 38 valid SLE samples (47 percent) presented overexpression (R>1) of at least one cytokine. Lesional skin samples tended to show higher cytokine expression than samples from uninvolved skin (p = 0.06). IL-5 and IFN-γ were the most commonly overexpressed cytokines. Samples with cytokine overexpression corresponded to more extensive and severe lesions. Prednisone dose did not differ between samples without cytokine overexpression (15.71±3.45 mg/day) and those with overexpressed cytokines (12.68±5.41 mg/day) (p = 0.216). Samples from all patients not receiving diphosphate chloroquine had at least one overexpressed cytokine. CONCLUSIONS: The heterogeneous keratinocyte cytokine gene expression reflects the complex immunological and inflammatory background in SLE. Patients with severe/extensive skin lesions showed a higher frequency of cytokine gene overexpression. Increased IFN-γ and IL-5 expression suggests that Th1 and Th2 cells are involved in SLE skin inflammation. The possibility that prednisone and antimalarial drugs may have contributed to low cytokine gene expression in some samples cannot be ruled out.
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Citocinas/genética , Expressão Gênica/genética , Queratinócitos/metabolismo , Lúpus Eritematoso Sistêmico/genética , Dermatopatias/genética , Citocinas/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Dermatopatias/metabolismoRESUMO
AIM: To evaluate the overlap of autoimmune hepatitis in hepatitis C virus (HCV)-infected patients with intense interface hepatitis. METHODS: Among 1759 patients with hepatitis C submitted to liver biopsy, 92 (5.2%) presented intense interface hepatitis. These patients were evaluated regarding the presence of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA) and anti-liver/kidney microsomal antibody (LKM-1), levels of gamma-globulin and histological findings related to autoimmune hepatitis (plasma cell infiltrate and presence of rosettes). RESULTS: Among patients with hepatitis C and intense interface hepatitis there was a low prevalence of autoantibodies (ANA = 12%, SMA = 5%, LKM-1 = 0%) and the median gamma-globulin level was within the normal range. Typical histological findings of autoimmune disease were observed in only two cases (2%). After applying the score for diagnosis of autoimmune hepatitis, only one patient was classified with a definitive diagnosis of autoimmune hepatitis. Since overlap with autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis C we sought to identify the variables associated with this finding. The presence of intense interface hepatitis was associated with more advanced age, both at the time of infection and at the time of the biopsy, and higher prevalence of blood transfusion and alcohol abuse. CONCLUSION: Although possible, overlap with autoimmune hepatitis is a very rare association in HCV-infected patients with intense interface hepatitis, an unusual presentation which seems to be related to other host variables.
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Hepatite C/fisiopatologia , Hepatite Autoimune/fisiopatologia , Adulto , Autoanticorpos/sangue , Biópsia , Feminino , Hepatite C/sangue , Hepatite C/imunologia , Hepatite C/patologia , Hepatite Autoimune/sangue , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Introdução: Complicações tromboembólicas são importantes fatores de risco para perda do enxerto e pior evolução após o transplante renal. pacientes com defeito trombofílico apresentam maior risco de complicações tromboembólicas. Foram analisados, entre receptores de transplante renal, a prevalência de defeito trombofílico e o risco atribuído a esta condição para a perda do enxerto e para o desenvolvimento de tromboses intravasculares. Métodos: estudo do tipo coorte incluindo 388 receptores adultos analisados quanto à presença de trombofilia de acordo com a pesquisa de anticorpos anticardiolipidina (aCL) por ELISA e das mutações G1691A no gene do fator V (FV) e G20210A no gene da protrombina (PT) por PCR multiplex. Resultados: Defeito trombofílico foi identificado em 25,8% dos pacientes. As taxas de sobrevida de 2 anos do enxerto foram semelhantes entre os pacientes com e sem defeito trombofílico (94%, p=0,53), bem como a sobrevida dos enxertos livres de tromboses intravasculares (97% versus 97%, p=0,83). pacientes com defeito trombofílico apresentaram prevalência de tromboses intravasculares semelhante à do grupo-controle (3% versus 3,5%, p=0,82). O transplante renal anterior foi associado a maior risco de perda de enxerto (OR 20,8, p<0,001) e de ocorrência de trombose intravasculares (OR 6,8, p=0,008). Conclusões: As prevalências das mutações FVG1691A e PTG20210A na população estudada foram semelhantes às da população geral não transplantada, e a prevalência de anticorpos aCL superou a observada entre os indivíduos sadios. Não houve associação entre os marcadores de trombofilia estudados e a sobrevida em médio prazo do transplante renal.
Introduction: Thromboembolic complications are important risk factors for graft loss and poor outcome after renal transplantation. patients with thrombophilic defects are at increased risk of thromboembolic complications. Were analyzed, among kidney transplant recipients, the prevalence of thrombophilic defects and the risk attributed to this condition for graft loss and the development of intravascular thrombosis. Methods: A cohort study including 388 adult recipients analyzed for the presence of thrombophilia according to anticardiolipidina antibodies (aCL) by ELISA and gene mutations G1691A in factor V (FV) and prothrombin gene G20210A (PT) by multiplex PCR. Results: thrombophilic defect was identified in 25.8% of patients. The survival rates of two years of the graft were similar between patients with and without thrombophilic defect (94%, p = 0.53), and the survival of free grafts of intravascular thrombosis (97% versus 97%, p = 0 , 83). patients with an increased prevalence of thrombophilic defect intravascular thrombosis similar to the control group (3% versus 3.5%, p = 0.82). Previous renal transplantation was associated with increased risk of graft loss (OR 20.8, p <0.001) and intravascular thrombosis (OR 6.8, p = 0.008). Conclusions: The prevalence of mutations and FVG1691A PTG20210A in this study were similar to those of the general population not transplanted, and the prevalence of aCL antibodies exceeded that observed among healthy individuals. There was no association between markers of thrombophilia studied and medium-term survival in renal transplantation.
Assuntos
Humanos , Masculino , Feminino , Adulto , Anticorpos Anticardiolipina/análise , Anticorpos Anticardiolipina/genética , Fator V/genética , Modelos Logísticos , Análise de Sobrevida , Trombofilia/complicações , Trombofilia/diagnóstico , Trombofilia/patologia , Transplante de RimRESUMO
OBJECTIVE: T cell receptor excision circle (TREC) is produced during T cell maturation within the thymus, and the number of TREC-bearing cells reflects the proportion of recent thymic emigrants in the peripheral lymphocyte pool. We studied TREC levels in peripheral CD4+ and CD8+ lymphocytes in patients with systemic lupus erythematosus (SLE) with quiescent and with active disease and in age- and sex-matched healthy volunteers. METHODS: TREC levels in peripheral CD4+ and CD8+ lymphocytes were determined in 29 patients with quiescent SLE, in 22 with active disease, and in 31 age- and sex-matched healthy volunteers. The number of TREC/microg DNA was determined by real-time polymerase chain reaction gauged by a standard curve with known number of TREC-containing plasmids. RESULTS: TREC levels in CD4+ and CD8+ cells were lower in patients with active SLE (2.27 +/- 2.05 x 10(4) and 4.14 +/- 4.06 x 10(4) TREC/microg DNA, respectively) compared to quiescent SLE (5.83 +/- 7.41 x 10(4) and 11.24 +/- 15.06 x 10(4) TREC/microg DNA; p = 0.03, p = 0.02, respectively). Patients with active SLE had lower TREC levels in CD4+ T cells than controls (2.27 +/- 2.05 x 10(4) vs 5.64 +/- 4.99 x 10(4) TREC/microg DNA; p = 0.03), but this difference did not reach statistical significance for CD8+ cells (4.14 +/- 4.06 x 10(4) vs 8.77 +/- 8.78 x 10(4) TREC/microg DNA; p = 0.1). Patients with quiescent SLE presented TREC levels similar to controls in CD4+ and CD8+ cells (p = 0.49, p = 0.3, respectively). CONCLUSION: Our results reveal decreased TREC levels in the peripheral blood of patients with active but not in patients with quiescent SLE. These data suggest that TREC levels are affected by disease activity in SLE.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Timo/imunologia , Adolescente , Adulto , Movimento Celular , Feminino , Rearranjo Gênico do Linfócito T/genética , Rearranjo Gênico do Linfócito T/imunologia , Humanos , Lúpus Eritematoso Sistêmico/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Adulto JovemRESUMO
A síndrome de Werner é uma doença autossômica recessiva rara associada a envelhecimento precoce, cujo quadro cutâneo deve ser distinguido daquele encontrado na esclerose sistêmica (ES). Descrevemos aqui o caso de uma paciente de 39 anos de idade, portadora de síndrome de Werner, encaminhada ao nosso serviço com hipótese diagnóstica inicial de ES. A paciente apresentava várias manifestações associadas à síndrome de Werner, incluindo cabelos precocemente grisalhos, voz estridente, baixa estatura, alterações cutâneas esclerodermiformes, diabetes melito, catarata, hipogonadismo, hipotireoidismo e hiperlipidemia. Não apresentava fenômeno de Raynaud, manifestações viscerais típicas da ES, alterações capilaroscópicas periungueais ou auto-anticorpos. O diagnóstico de síndrome de Werner, apesar de raro, deve ser lembrado no diagnóstico diferencial de ES, principalmente na presença de manifestações atípicas e na ausência de alterações típicas da ES.
Werner's syndrome is a rare autosomal recessive disease associated with premature ageing. Skin alteration must be distinguished from cutaneous manifestation of systemic sclerosis (SSc). We describe a case of a 39 years old patient with Werner's syndrome admitted with an initial diagnostic hypothesis of SSc. The patient had many characteristic features associated with Werner's syndrome including gray hair, hoarseness, short stature, scleroderma-like skin changes, diabetes mellitus, cataracts, hypogonadism, hypothyroidism, and hyperlipidemia. There was no Raynaud's phenomenon, other typical visceral manifestation of SSc, nailfold capillary alterations or autoantibodies. Werner's syndrome diagnosis notwithstanding rare, should be remember in the differential diagnosis of SSc, mainly in the presence of atypical manifestations and in the absence of typical features of SSc.
Assuntos
Humanos , Feminino , Adulto , Senilidade Prematura , Progéria , Escleroderma Sistêmico , Síndrome de WernerRESUMO
Os repetidos episódios de isquemia-reperfusão observados na esclerose sistêmica (ES) acarretam aumento na atividade de radicais livres, o que pode estar implicado nas anormalidades vasculares e inflamatórias descritas nessa enfermidade. A N-acetilcisteína sob forma endovenosa é uma potente droga antioxidante e, como tal, poderia ter efeito benéfico para o tratamento das lesões vasculares da ES. Relatamos o tratamento com N-acetilcisteína endovenosa de três pacientes com diagnóstico de ES e com úlceras ativas de extremidades (dígitos ou artelhos). Dois pacientes apresentavam duas úlceras digitais e o terceiro paciente, três úlceras em artelhos no início do tratamento. Todos os pacientes apresentaram diminuição no diâmetro de pelo menos uma úlcera após o tratamento. Duas pacientes apresentaram cicatrização de uma úlcera. Esses resultados preliminares sugerem que a N-acetilcisteína endovenosa parece ser uma boa opção terapêutica para o tratamento de úlceras de extremidades em pacientes com ES e justificam a elaboração de ensaios controlados duplo-cego com placebo.
Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Acetilcisteína , Doença de Raynaud , Doenças Reumáticas , Escleroderma SistêmicoRESUMO
Objetivos: Avaliar a eficácia do losartan no tratamento do fenômeno de Raynaud (FRy) em pacientes com FRy secundário à esclerose sistêmica (ES). Avaliamos também as anormalidades bioquímicas da microcirculação, através de dosagem da lacticemia de polpa digital associada a um estímulo frio (LPD-EF) e às anormalidades anatômicas da microcirculação, através da capilaroscopia periungueal (CPU), antes e após a intervenção terapêutica, buscando possíveis correlações com a ação do losartan no nível microvascular. Métodos: Trata-se de um estudo aberto em que foram selecionados consecutivamente dez pacientes com diagnóstico de ES e FRy presentes na seleção. Sete pacientes receberam losartan 50 mg/dia e três, 100 mg/dia VO por quatro semanas. Os pacientes foram avaliados quanto à eficácia da droga, através de questionários aplicados no dia 0 e ao término das semanas 1, 2, 3, e 4. Capilaroscopia periungueal e o teste da LPD-EF foram realizados no início e ao final do estudo. Resultados: Observamos melhora significativa na escala de gravidade do FRy ao analisarmos as semanas 0 a 4 (p=0,048). Em relação à escala visual analógica da dor, ao número de ataques de FRy por dia e à duração estimada dos ataques, observamos queda nos parâmetros analisados entre as semanas 0 a 4, mas tal diminuição não alcançou diferença significante. Não houve diferença significativa em relação aos parâmetros analisados pela CPU e aos valores de LPD entre as semanas 0 e 4. Conclusões: O losartan parece apresentar benefício terapêutico discreto ou moderado em pacientes com FRy secundário à ES, não modificando os parâmetros morfológicos ou bioquímicos da microcirculação.