RESUMO
Background: Diabetes mellitus type 1 (T1DM) is one of the childhood diseases with growing prevalence. Various accompanying autoimmune diseases were seen with type 1 diabetes. The most common autoimmune diseases with T1DM are autoimmune thyroiditis and celiac disease. In some reports, autoimmune hepatitis has been reported in association with DM-1. Objectives: The aim of this study was to evaluate autoimmune hepatitis autoantibodies in children with T1DM. Materials and methods: In this crosssectional study, 202 children with T1DM were evaluated (47.5% were males and 52.5% were girls). Liver enzymes, autoimmune hepatitis related autoantibodies such as anti-nuclear antibodies (ANA), anti-smooth muscle (ASMA) and anti liver and kidney microsomal antibodies (LKM-1) were measured. Liver ultrasound was done for participants and biopsy of liver was taken for children with increased echogenicity of the liver, hepatomegaly or elevated liver enzymes. Results analyzed by statistical software spss-16, Descriptive statistics and chi-square test, paired T-TEST. Level of less than 5% was considered statistically significant. Results: In 6 patients ANA and in 4 patients (2%) ASMA was positive,1 patient was ASMA positive but ANA negative. None of the patients were Anti LKM-1 positive. 3 patients had positive ANA and ASMA, and increased liver echogenicity on ultrasound simultaneously. Histological evaluation was showed that 2 patients had findings in favor of autoimmune hepatitis. Conclusion: Auto antibodies were positive in 10 cases. ANA was positive in 6 (2.97%) of all cases. ASMA was positive in 4 (1.98%) cases. Increased echogenicity was found in 3 cases. Histological evaluation showed 2 patients had biopsy confirmed autoimmune hepatitis. AIH-2 was not seen among our cases.
Antecedentes: La diabetes mellitus tipo 1 (DM1) es una de las enfermedades infantiles con mayor prevalencia. Se observaron varias enfermedades autoinmunes acompañantes con diabetes tipo 1. Las enfermedades autoinmunes más comunes con DM1 son la tiroiditis autoinmune y la enfermedad celíaca. En algunos reportes, se ha encontrado hepatitis autoinmune en asociación con DM-1. Objetivos: El objetivo de este estudio fue evaluar los autoanticuerpos de hepatitis autoinmunes en niños con DM1. Materiales y métodos: En este estudio transversal, se evaluaron 202 niños con DM1 (47,5% eran hombres y 52,5% eran niñas). Se midieron las enzimas hepáticas, los autoanticuerpos autoinmunes relacionados con la hepatitis, como los anticuerpos antinucleares (ANA), el músculo liso (ASMA) y los anticuerpos microsomales hepáticos y renales (LKM-1). Se realizó una ecografía hepática para los participantes y se tomó una biopsia del hígado para niños con mayor ecogenicidad del hígado, hepatomegalia o enzimas hepáticas elevadas. Los resultados fueron analizados por el software estadístico spss-16 usando estadística descriptiva y prueba de chi-cuadrado, T-TEST pareado. Se consideró estadísticamente significativo un nivel menor del 5%. Resultados: En 6 pacientes con ANA y en 4 pacientes (2%) ASMA fue positiva, 1 paciente fue ASMA positiva pero ANA negativa. Ninguno de los pacientes fue anti LKM-1 positivo. 3 pacientes tuvieron ANA y ASMA positivas, y aumentaron la ecogenicidad hepática en la ecografía simultáneamente. La evaluación histológica mostró que 2 pacientes tenían hallazgos a favor de la hepatitis autoinmune. Conclusión: Los autoanticuerpos fueron positivos en 10 casos. ANA fue positivo en 6 (2,97%) de todos los casos. La ASMA fue positiva en 4 (1,98%) casos. Se encontró mayor ecogenicidad en 3 casos. La evaluación histológica mostró que 2 pacientes tenían biopsia confirmada de hepatitis autoinmune. AIH-2 no fue visto entre nuestros casos.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Adulto Jovem , Autoanticorpos/sangue , Hepatite Autoimune/imunologia , Diabetes Mellitus Tipo 1/imunologia , Aspartato Aminotransferases/sangue , Microssomos Hepáticos/imunologia , Anticorpos Antinucleares/sangue , Estudos Transversais , Alanina Transaminase/sangue , Rim/imunologia , Microssomos/imunologia , Músculo Liso/imunologiaRESUMO
BACKGROUND: Diabetes mellitus type 1 (T1DM) is one of the childhood diseases with growing prevalence. Various accompanying autoimmune diseases were seen with type 1 diabetes. The most common autoimmune diseases with T1DM are autoimmune thyroiditis and celiac disease. In some reports, autoimmune hepatitis has been reported in association with DM-1. OBJECTIVES: The aim of this study was to evaluate autoimmune hepatitis autoantibodies in children with T1DM. MATERIALS AND METHODS: In this crosssectional study, 202 children with T1DM were evaluated (47.5% were males and 52.5% were girls). Liver enzymes, autoimmune hepatitis related autoantibodies such as anti-nuclear antibodies (ANA), anti-smooth muscle (ASMA) and anti liver and kidney microsomal antibodies (LKM-1) were measured. Liver ultrasound was done for participants and biopsy of liver was taken for children with increased echogenicity of the liver, hepatomegaly or elevated liver enzymes. Results analyzed by statistical software spss-16, Descriptive statistics and chi-square test, paired T-TEST. Level of less than 5% was considered statistically significant. RESULTS: In 6 patients ANA and in 4 patients (2%) ASMA was positive,1 patient was ASMA positive but ANA negative. None of the patients were Anti LKM-1 positive. 3 patients had positive ANA and ASMA, and increased liver echogenicity on ultrasound simultaneously. Histological evaluation was showed that 2 patients had findings in favor of autoimmune hepatitis. CONCLUSION: Auto antibodies were positive in 10 cases. ANA was positive in 6 (2.97%) of all cases. ASMA was positive in 4 (1.98%) cases. Increased echogenicity was found in 3 cases. Histological evaluation showed 2 patients had biopsy confirmed autoimmune hepatitis. AIH-2 was not seen among our cases.
Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/imunologia , Hepatite Autoimune/imunologia , Adolescente , Alanina Transaminase/sangue , Anticorpos Antinucleares/sangue , Aspartato Aminotransferases/sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Rim/imunologia , Masculino , Microssomos/imunologia , Microssomos Hepáticos/imunologia , Músculo Liso/imunologia , Adulto JovemRESUMO
BACKGROUND: One of the undesirable complications that might occur after breast augmentation with silicone implants is capsular contracture. In its etiology, the relations between mast cells and myofibroblasts play an important role in collagen synthesis. Mast cells are able to activate fibroblasts into myofibroblasts, through paracrine secretions, inducing collagen production. The objectives of this study were to analyze the myofibroblast concentration through the α-SMA immunomarker and evaluate the intensity of mast cell expression against the C-Kit immunomarker. MATERIAL AND METHOD: Sixty-four Wistar rats were used, divided into two groups (polyurethane foam and textured surface) with 32 animals in each. The animals received silicone implants on the back, below the panniculus carnosus, and after the determined period, they were killed and the capsules formed around the implants were studied. The capsules were analyzed employing the immunohistochemical technique, with the α-SMA and C-Kit immunomarkers in subgroups of 30, 50, 70 and 90 days. RESULTS: The myofibroblast concentration was higher in the polyurethane group when compared to the textured group (30 days p = 0.105; 50 days p = 0.247; 70 days p = 0.014 and 90 days p = 0.536). The intensity of mast cell expression was more pronounced in the polyurethane group when compared to the textured group (30 days p = 0.798; 50 days p = 0.537; 70 days p = 0.094 and 90 days p = 0.536). CONCLUSIONS: Polyurethane-coated implants induced higher concentrations of myofibroblasts and higher expression of mast cells, when compared to the textured surface implants. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Actinas/imunologia , Implante Mamário/efeitos adversos , Contratura Capsular em Implantes/patologia , Poliuretanos/efeitos adversos , Proteínas Proto-Oncogênicas c-kit/imunologia , Géis de Silicone/efeitos adversos , Animais , Biomarcadores/metabolismo , Implante Mamário/métodos , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Contratura Capsular em Implantes/etiologia , Músculo Liso/imunologia , Músculo Liso/patologia , Fotomicrografia/métodos , Distribuição Aleatória , Ratos , Ratos Wistar , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To evaluate autoimmune hepatitis (AIH) in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. METHODS: This retrospective multicenter study included 847 patients with cSLE, performed in 10 Pediatric Rheumatology services of São Paulo state, Brazil. AIH was defined according to the International Autoimmune Hepatitis Group criteria (IAHGC). The statistical analysis was performed using the Bonferroni's correction (p < 0.0033). RESULTS: AIH in cSLE patients confirmed by biopsy was observed in 7/847 (0.8%) and all were diagnosed during adolescence. The majority occurred before or at cSLE diagnosis [5/7 (71%)]. Antinuclear antibodies were a universal finding, 43% had concomitantly anti-smooth muscle antibodies and all were seronegative for anti-liver kidney microsomal antibodies. All patients with follow-up ≥18 months (4/7) had complete response to therapy according to IAHGC. None had severe hepatic manifestations such as hepatic failure, portal hypertension and cirrhosis at presentation or follow-up. Further comparison of 7 cSLE patients with AIH and 28 without this complication with same disease duration [0 (0-8.5) vs. 0.12 (0-8.5) years, p = 0.06] revealed that the frequency of hepatomegaly was significantly higher in cSLE patients in the former group (71% vs. 11%, p = 0.003) with a similar median SLEDAI-2 K score [6 (0-26) vs. 7 (0-41), p = 0.755]. No differences were evidenced regarding constitutional involvement, splenomegaly, serositis, musculoskeletal, neuropsychiatric and renal involvements, and treatments in cSLE patients with and without AIH (p > 0.0033). CONCLUSIONS: Overlap of AIH and cSLE was rarely observed in this large multicenter study and hepatomegaly was the distinctive clinical feature of these patients. AIH occurred during adolescence, mainly at the first years of lupus and it was associated with mild liver manifestations.
Assuntos
Hepatite Autoimune/epidemiologia , Hepatomegalia/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Adolescente , Idade de Início , Anticorpos Antinucleares/análise , Autoantígenos/análise , Brasil/epidemiologia , Criança , Feminino , Hepatite Autoimune/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Microssomos/imunologia , Músculo Liso/imunologia , Estudos RetrospectivosRESUMO
BACKGROUND: We identified a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America, which we term El Bagre-EPF, and observed reactivity to arrector pili muscle (APM), thus we tested for autoimmunity to APM. METHODS: We took skin biopsies from 30 patients with El Bagre-EPF and 30 healthy controls (HCs) matched by age, sex and occupation, who were all from the endemic area, and tested these using direct immunofluorescence (DIF), confocal microscopy, immunohistochemistry and immunoblotting (IB). RESULTS: Of the 30 patients with El Bagre-EPF, 27 had autoantibodies to APM that colocalized with commercial antibodies to myocardium-enriched zonula occludens-1-associated protein (MYZAP), desmoplakin (DP)1 and DP2, plakophilin 4, and Armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) (P < 0.001, Fisher exact test). The positive staining also colocalized with Junctional Adhesion Molecule 1 (JAM-A), a control antibody for gap cell junctions. No HC samples were positive. In 27 of the 30 patients, serum that was APM-positive also displayed IB colocalization of their autoantibody molecular weights with the Progen antibodies (P < 0.001, Fisher exact test). CONCLUSIONS: Patients affected by El Bagre-EPF have autoantibodies to APM, colocalizing with the antibodies MYZAP, ARVCF, p0071, DP1 and DP2, suggesting that these molecules are El Bagre-EPF antigens. Further, all of these antigens represent components of cell junctions, indicating that the immune response is directed, at least partially, against cell junctions. The immune response in patients affected by El Bagre-EPF is polyclonal, and it includes B and T lymphocytes, mast cells, IgG, IgA, IgM, IgD, IgE, fibrinogen, albumin, complement/C1q, C3c and C4.
Assuntos
Autoanticorpos/sangue , Autoimunidade , Doenças Endêmicas , Músculo Liso/imunologia , Pênfigo/imunologia , Proteínas do Domínio Armadillo/imunologia , Moléculas de Adesão Celular/imunologia , Colômbia , Desmoplaquinas/imunologia , Humanos , Immunoblotting , Imuno-Histoquímica , Pênfigo/patologia , Fosfoproteínas/imunologia , Placofilinas/imunologia , Receptores de Superfície Celular/imunologia , Proteína da Zônula de Oclusão-1/imunologiaRESUMO
UNLABELLED: Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). CONCLUSION: With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity.
Assuntos
Actinas/imunologia , Anticorpos Anti-Idiotípicos/sangue , Hepatite Autoimune/diagnóstico , Músculo Liso/imunologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Seguimentos , Hepatite Autoimune/metabolismo , Hepatite Autoimune/fisiopatologia , Humanos , Fígado/enzimologia , Fígado/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Organ-specific autoimmune diseases may appear in patients with systemic lupus erythematosus (SLE). Gastrointestinal symptoms are well documented in SLE and may be similar to those related to autoimmune gastrointestinal diseases. OBJECTIVE: Our aim was to search for gastrointestinal organ-specific autoantibodies in 194 patients with systemic lupus and 103 healthy controls from Southern Brazil. Methods Anti-endomysium antibodies (IgA-EmA), anti-gastric parietal cells (GPC) antibodies, anti-smooth muscle antibodies (ASMA), anti-mitochondrial antibodies (AMA) and anti-LKM-1 (liver-kidney microsomal) were searched for using indirect immunofluorescence in the sera of patients and controls. RESULTS: The total positivity of antibodies in SLE patients was 14.4% (28/194) and differed significantly from healthy individuals (0.97%; p<0.001). IgA-EmA was more common in lupus patients than in controls (11/194; p=0.009), and one of these patients had dermatitis herpetiformis. Clinical association revealed that IgA-EmA was more common in SLE patients with discoid lesions. The frequency of anti-GPC (p=0.10), ASMA (p=0.16) and AMA (p=0.55) did not differ significantly between groups. No patient presented LKM-1 autoantibodies. One patient presenting anti-GPC was diagnosed with atrophic gastritis and pernicious anemia. CONCLUSION: Only IgA-EmA was significantly associated with lupus and with the presence of discoid lesions. Until now, no obvious association with celiac disease has been found.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Gastroenteropatias/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Idoso , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/imunologia , Células Parietais Gástricas/imunologiaRESUMO
Non-organ-specific autoantibodies (NOSA) are well-recognized diagnostic markers of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but can also be observed in patients with viral hepatitis as well as in healthy subjects. The aim of this study was to evaluate the prevalence of NOSA in subjects living in a rural community in Brazil and to correlate their occurrence with the presence of liver disease. Seven hundred twenty-five apparently healthy subjects were randomly selected for assessment of antinuclear (ANA), anti-smooth muscle (SMA), antimitochondrial (AMA), anti-liver/kidney microsome type 1, and anti-liver cytosol type 1 antibodies. Subjects with those NOSA were evaluated for the presence of AIH, PBC, and viral hepatitis. Reactivities for all NOSA, SMA, ANA, and AMA were detected, respectively, in 14, 10, 4, and 0.1% of subjects, with a mean titer of 1:40. NOSA-positive subjects were significantly older and more frequently females. No correlation was observed between the occurrence of NOSA and PBC, AIH, or viral hepatitis. The prevalence of NOSA in Brazilians was 14%. They were usually low titer. NOSA were more frequently observed in females and older subjects and their presence was not correlated with the presence of AIH, PBC, or viral hepatitis.
Assuntos
Autoanticorpos/imunologia , Hepatite Autoimune/imunologia , Hepatite Viral Humana/imunologia , Cirrose Hepática Biliar/imunologia , População Rural/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/imunologia , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/epidemiologia , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/epidemiologia , Humanos , Lactente , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/epidemiologia , Masculino , Mitocôndrias/imunologia , Músculo Liso/imunologia , Prevalência , Adulto JovemRESUMO
Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8% and cryoglobulinemia was demonstrated in 36.9% patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.
Assuntos
Autoanticorpos/análise , Autoimunidade/imunologia , Crioglobulinemia/imunologia , Hepatite C Crônica/imunologia , Cirrose Hepática/virologia , Músculo Liso/imunologia , Adulto , Idoso , Autoanticorpos/imunologia , Biomarcadores/análise , Biópsia , Portador Sadio/imunologia , Crioglobulinemia/complicações , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8 percent and cryoglobulinemia was demonstrated in 36.9 percent patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Autoanticorpos/análise , Autoimunidade/imunologia , Crioglobulinemia/imunologia , Hepatite C Crônica/imunologia , Cirrose Hepática/virologia , Músculo Liso/imunologia , Autoanticorpos/imunologia , Biópsia , Biomarcadores/análise , Portador Sadio/imunologia , Crioglobulinemia/complicações , Técnica Indireta de Fluorescência para Anticorpo , Hepatite C Crônica/complicações , Cirrose Hepática/imunologia , Cirrose Hepática/patologiaRESUMO
BACKGROUND: Clustering of autoimmune diseases is common and may be due to genetic background and exposition to environmental triggers. OBJECTIVE: The aim is to carry out a laboratory and clinical study of the prevalence of gastrointestinal organ-specific autoantibodies in rheumatoid arthritis (RA) patients and their relatives. METHODS: Serum samples of 156 RA patients, 200 relatives, and 100 healthy controls were studied for anti-smooth muscle antibody (ASMA), anti-mitochondrial (AMA), anti-parietal cell (APCA), anti-liver-kidney microsome (LKM), and anti-endomysium antibodies (IgA-EmA) by indirect immunofluorescence. RESULTS: A total of eight out of the 156 (5.1%) RA patients were positive for the autoantibodies (ASMA = 1; AMA = 2, APCA = 5). In the relative group, 12/200 (6%) had at least one positive autoantibody (ASMA = 1; AMA = 2, APCA = 7, IgA-EmA = 2). In the control group, two out of the 100 (2%) healthy controls were positive (ASMA = 1, APCA = 1). No statistical difference was found between RA patients, their relatives, and controls in relation to the frequency of autoantibodies evaluated. CONCLUSION: Although RA patients and their relatives have positivity of AMA, ASMA, and APCA without statistical difference in relation to healthy individuals, the findings may be of value for adequate clinical approach of these subjects.
Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/terapia , Autoanticorpos/química , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Adulto , Idoso , Saúde da Família , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Trato Gastrointestinal/imunologia , Humanos , Rim/imunologia , Masculino , Microssomos Hepáticos/imunologia , Pessoa de Meia-Idade , Mitocôndrias/imunologia , Músculo Liso/imunologia , Células Parietais Gástricas/imunologiaRESUMO
INTRODUCTION: Erectile dysfunction is considered an early clinical manifestation of vascular disease and an independent risk factor for cardiovascular events associated with endothelial dysfunction and increased levels of pro-inflammatory cytokines. Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, suppresses endothelial nitric oxide synthase (eNOS) expression. AIM: Considering that nitric oxide (NO) is of critical importance in penile erection, we hypothesized that blockade of TNF-alpha actions would increase cavernosal smooth muscle relaxation. METHODS: In vitro organ bath studies were used to measure cavernosal reactivity in wild type and TNF-alpha knockout (TNF-alpha KO) mice and NOS expression was evaluated by western blot. In addition, spontaneous erections (in vivo) were evaluated by videomonitoring the animals (30 minutes). Collagen and elastin expression were evaluated by Masson trichrome and Verhoff-van Gieson stain reaction, respectively. MAIN OUTCOME MEASURES: Corpora cavernosa from TNF-alpha KO mice exhibited increased NO-dependent relaxation, which was associated with increased eNOS and neuronal NOS (nNOS) cavernosal expression. RESULTS: Cavernosal strips from TNF-alpha KO mice displayed increased endothelium-dependent (97.4 +/- 5.3 vs. CONTROL: 76.3 +/- 6.3, %) and nonadrenergic-noncholinergic (93.3 +/- 3.0 vs. CONTROL: 67.5 +/- 16.0; 16 Hz) relaxation compared to control animals. These responses were associated with increased protein expression of eNOS and nNOS (P < 0.05). Sympathetic-mediated (0.69 +/- 0.16 vs. CONTROL: 1.22 +/- 0.22; 16 Hz) as well as phenylephrine-induced contractile responses (1.6 +/- 0.1 vs. CONTROL: 2.5 +/- 0.1, mN) were attenuated in cavernosal strips from TNF-alpha KO mice. Additionally, corpora cavernosa from TNF-alpha KO mice displayed increased collagen and elastin expression. In vivo experiments demonstrated that TNF-alpha KO mice display increased number of spontaneous erections. CONCLUSION: Corpora cavernosa from TNF-alpha KO mice display alterations that favor penile tumescence, indicating that TNF-alpha plays a detrimental role in erectile function. A key role for TNF-alpha in mediating endothelial dysfunction in ED is markedly relevant since we now have access to anti-TNF-alpha therapies.
Assuntos
Disfunção Erétil/imunologia , Disfunção Erétil/terapia , Músculo Liso/imunologia , Fator de Necrose Tumoral alfa/imunologia , Vasodilatação/fisiologia , Animais , Colágeno/metabolismo , Elastina/metabolismo , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Disfunção Erétil/metabolismo , Masculino , Camundongos , Camundongos Knockout , Músculo Liso/metabolismo , Músculo Liso/patologia , Óxido Nítrico Sintase/metabolismo , PênisRESUMO
BACKGROUND/AIM: Smooth muscle antibody (SMA) specific for the protein actin, a major component of the cytoskeleton of epithelial cells, is one of the most prevalent non-organ specific autoantibodies in the serum of celiac disease (CD) patients. Our aim was to explore the clinical relevance of the presence of IgA type anti-actin antibody (AAA) and SMA in a series of patients with CD. METHODS: We evaluated frozen serum samples collected at diagnosis from 92 adult patients with CD and 52 control individuals in whom CD was excluded. Patients were re-evaluated a median time of 5 yr after treatment. IgA type AAA was detected using a modified commercial ELISA assay and IgA SMA was detected using indirect immunofluorescence on primate esophagus substrate. RESULTS: At diagnosis, samples from CD patients had significantly higher AAA values than controls (p<0.00001). While all active CD patients had serum AAA values over the cut-off for healthy controls, we observed a very significant reduction of these antibodies after treatment (p>0.0001). AAA had a highly significant correlation with both, tissue, transglutaminase (r=0.62) and antigliadin (r=0.60, p<0.00001) antibodies as well as the severity of the intestinal injury (p<0.05). SMA was detected in sera of 35 consecutive CD patients. At diagnosis, SMA positive patients had significantly higher values of AAA (p<0.0002), increased number of autoimmune disorders (p<0.04), delayed menarche (p<0.04), lower hemoglobin levels (p<0.01), increased fecal a-I antitrypsin clearance (p<0.01) and more severe diarrhea (p<0.06). We also detected a trend to more severe complications at follow-up (p=0.059). CONCLUSIONS: Based on our findings we suggest that the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients with a potential relevance to diagnosis and follow-up. The presence of SMA seems to define a distinct subset of CD patients with a more severe clinical outcome.
Assuntos
Actinas/imunologia , Autoanticorpos/sangue , Doença Celíaca/imunologia , Imunoglobulina A/sangue , Músculo Liso/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Celíaca/diagnóstico , Doença Celíaca/dietoterapia , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
BACKGROUND/AIM: Smooth muscle antibody (SMA) specific for the protein actin, a major component of the cytoskeleton of epithelial cells, is one of the most prevalent non-organ specific autoantibodies in the serum of celiac disease (CD) patients. Our aim was to explore the clinical relevance of the presence of IgA type anti-actin antibody (AAA) and SMA in a series of patients with CD. METHODS: We evaluated frozen serum samples collected at diagnosis from 92 adult patients with CD and 52 control individuals in whom CD was excluded. Patients were re-evaluated a median time of 5 yr after treatment. IgA type AAA was detected using a modified commercial ELISA assay and IgA SMA was detected using indirect immunofluorescence on primate esophagus substrate. RESULTS: At diagnosis, samples from CD patients had significantly higher AAA values than controls (p<0.00001). While all active CD patients had serum AAA values over the cut-off for healthy controls, we observed a very significant reduction of these antibodies after treatment (p>0.0001). AAA had a highly significant correlation with both, tissue, transglutaminase (r=0.62) and antigliadin (r=0.60, p<0.00001) antibodies as well as the severity of the intestinal injury (p<0.05). SMA was detected in sera of 35 consecutive CD patients. At diagnosis, SMA positive patients had significantly higher values of AAA (p<0.0002), increased number of autoimmune disorders (p<0.04), delayed menarche (p<0.04), lower hemoglobin levels (p<0.01), increased fecal a-I antitrypsin clearance (p<0.01) and more severe diarrhea (p<0.06). We also detected a trend to more severe complications at follow-up (p=0.059). CONCLUSIONS: Based on our findings we suggest that the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients with a potential relevance to diagnosis and follow-up. The presence of SMA seems to define a distinct subset of CD patients with ...(AU)
Introduccion/objetivo: El anticuerpo anti-musculo liso (SMA) dirigido contra la proteína actina, un componente mayor del citoesqueleto de las células epiteliales, es el anticuerpo no-órgano específico más prevalente en enfermedad celíaca (EC). Nuestro objetivo fue explorar la importancia clínica de los anticuerpos anti-actina (AAA) y SMA en una serie de pacientes con EC. Métodos: Evaluamos 92 muestras serológicas de pacientes celíacos adultos recolectadas al momento del diagnóstico y la de 52 individuos controles no celíacos. Los pacientes fueron re-evaluados luego de un tiempo medio de 5 años en tratamiento. Evaluamos AAA tipoIgA mediante ELISA empleando un equipo commercial modificado y SMA IgA por inmunofluorescencia indirecta sobre sustrato de esófago de mono. Resultados: Al momento del diagnóstico, los pacientes celíacos tuvieron valores de AAA significativamente más elevados que los controles (p<0.00001). Todos los pacientes con EC activa presentaron niveles de AAA por encima del valor de corte determinado para el grupo control sano y se evidenció una reducción significativa de los nivelesluego del tratamiento (p>0.0001). Los AAA presentaron una correlación significativa con los anticuerpos anti-transglutaminasa tisular (r=0.62) y anti-gliadina (r=0.60) (p<0.00001), de igual modo que con la severidad del daño intestinal (p<0.05). Al momento del diagnóstico, se detectó SMA en el suero de 35 pacientes no controles. Los pacientes SMA positivos tuvieron valores significativamente mayores de AAA (p<0.002), un incremento del número de enfermedades autoinmunes asociadas (p<0.04), menarca tardía (p<0.04), niveles bajos de hemoglobina (p<0.01), incremento del clearance de a-1 antitripsina fecal (p<0.01) y mayor severidad de la diarrea (p<0.06).En ellos se evidenció una tendencia al desarrollo de complicaciones más severas durante el seguimiento (p=0.059). Conclusiones: Sugerimos que la presencia de un valor sérico aumentado de AAA tipo IgA...(AU)
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Actinas/imunologia , Autoanticorpos/sangue , Doença Celíaca/imunologia , Imunoglobulina A/sangue , Músculo Liso/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Celíaca/diagnóstico , Doença Celíaca/dietoterapia , Ensaio de Imunoadsorção Enzimática , Técnica Indireta de Fluorescência para Anticorpo , Seguimentos , Índice de Gravidade de DoençaRESUMO
BACKGROUND/AIM: Smooth muscle antibody (SMA) specific for the protein actin, a major component of the cytoskeleton of epithelial cells, is one of the most prevalent non-organ specific autoantibodies in the serum of celiac disease (CD) patients. Our aim was to explore the clinical relevance of the presence of IgA type anti-actin antibody (AAA) and SMA in a series of patients with CD. METHODS: We evaluated frozen serum samples collected at diagnosis from 92 adult patients with CD and 52 control individuals in whom CD was excluded. Patients were re-evaluated a median time of 5 yr after treatment. IgA type AAA was detected using a modified commercial ELISA assay and IgA SMA was detected using indirect immunofluorescence on primate esophagus substrate. RESULTS: At diagnosis, samples from CD patients had significantly higher AAA values than controls (p<0.00001). While all active CD patients had serum AAA values over the cut-off for healthy controls, we observed a very significant reduction of these antibodies after treatment (p>0.0001). AAA had a highly significant correlation with both, tissue, transglutaminase (r=0.62) and antigliadin (r=0.60, p<0.00001) antibodies as well as the severity of the intestinal injury (p<0.05). SMA was detected in sera of 35 consecutive CD patients. At diagnosis, SMA positive patients had significantly higher values of AAA (p<0.0002), increased number of autoimmune disorders (p<0.04), delayed menarche (p<0.04), lower hemoglobin levels (p<0.01), increased fecal a-I antitrypsin clearance (p<0.01) and more severe diarrhea (p<0.06). We also detected a trend to more severe complications at follow-up (p=0.059). CONCLUSIONS: Based on our findings we suggest that the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients with a potential relevance to diagnosis and follow-up. The presence of SMA seems to define a distinct subset of CD patients with ...
Introduccion/objetivo: El anticuerpo anti-musculo liso (SMA) dirigido contra la proteína actina, un componente mayor del citoesqueleto de las células epiteliales, es el anticuerpo no-órgano específico más prevalente en enfermedad celíaca (EC). Nuestro objetivo fue explorar la importancia clínica de los anticuerpos anti-actina (AAA) y SMA en una serie de pacientes con EC. Métodos: Evaluamos 92 muestras serológicas de pacientes celíacos adultos recolectadas al momento del diagnóstico y la de 52 individuos controles no celíacos. Los pacientes fueron re-evaluados luego de un tiempo medio de 5 años en tratamiento. Evaluamos AAA tipoIgA mediante ELISA empleando un equipo commercial modificado y SMA IgA por inmunofluorescencia indirecta sobre sustrato de esófago de mono. Resultados: Al momento del diagnóstico, los pacientes celíacos tuvieron valores de AAA significativamente más elevados que los controles (p<0.00001). Todos los pacientes con EC activa presentaron niveles de AAA por encima del valor de corte determinado para el grupo control sano y se evidenció una reducción significativa de los nivelesluego del tratamiento (p>0.0001). Los AAA presentaron una correlación significativa con los anticuerpos anti-transglutaminasa tisular (r=0.62) y anti-gliadina (r=0.60) (p<0.00001), de igual modo que con la severidad del daño intestinal (p<0.05). Al momento del diagnóstico, se detectó SMA en el suero de 35 pacientes no controles. Los pacientes SMA positivos tuvieron valores significativamente mayores de AAA (p<0.002), un incremento del número de enfermedades autoinmunes asociadas (p<0.04), menarca tardía (p<0.04), niveles bajos de hemoglobina (p<0.01), incremento del clearance de a-1 antitripsina fecal (p<0.01) y mayor severidad de la diarrea (p<0.06).En ellos se evidenció una tendencia al desarrollo de complicaciones más severas durante el seguimiento (p=0.059). Conclusiones: Sugerimos que la presencia de un valor sérico aumentado de AAA tipo IgA...
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos , Actinas/imunologia , Doença Celíaca/imunologia , Imunoglobulina A/sangue , Músculo Liso/imunologia , Ensaio de Imunoadsorção Enzimática , Doença Celíaca/diagnóstico , Doença Celíaca/dietoterapia , Estudos de Casos e Controles , Biomarcadores/sangue , Seguimentos , Técnica Indireta de Fluorescência para Anticorpo , Índice de Gravidade de DoençaRESUMO
Toxocara vitulorum is a pathogenic nematode from the small intestine of very young buffalo calves. To understand the development of the inflammatory responses in the wall of the gut, samples of tissues were removed from the duodenum, jejunum and ileum of buffalo calves naturally infected with T. vitulorum during the beginning of the infection, at the peak of egg output, as well as during the periods of rejection of the worms and post-rejection. Two additional control groups of uninfected calves (by anti-helminthic therapy of their mothers and after the birth) were also necropsied on days 30 and 50 after birth. Blood samples were fortnightly collected from birth to 174 days post-birth. Blood smears were prepared and stained with Giemsa for eosinophils. The parasitological status of buffalo calves was evaluated through weekly fecal egg counts (EPG) from 1 to 106 days after birth, which revealed that T. vitulorum egg shedding started on day 11, reached the peak of the infection on day 49 and finally expelled the parasites between days 50 and 85 after birth. In the infected buffalo calves, the mast cell population increased significantly, by two-fold in the mucosa (villus-crypt unit (VCU)) of the duodenum and four-fold in the proximal jejunum; but these increases were statistically significant only at the peak of the infection. Although mast cell numbers increased in the mucosa of the ileum as well as in both the submucosal and muscle tissues of the duodenum, proximal jejunum and ileum, the data was not significantly different from the controls. Eosinophil numbers increased in the mucosa of the duodenum (two-five times higher than the control) and proximal jejunum (three-five-fold) during the period of the infection (beginning, peak and rejection). The relative numbers of eosinophils increased in the blood stream from the second to the seventh week. In conclusion, T. vitulorum infection elicited mastocytosis and tissue eosinophilia in the duodenum and proximal jejunum, as well as eosinophilia in the blood stream, during the beginning, at the peak and during the rejection of the worm. After the rejection of the worms, the numbers of these cells returned to normal levels suggesting that these cells may have a role in the process of rejection of T. vitulorum by the host.
Assuntos
Búfalos/imunologia , Búfalos/parasitologia , Eosinófilos/imunologia , Mucosa Intestinal/imunologia , Mastócitos/imunologia , Toxocaríase/sangue , Toxocaríase/imunologia , Animais , Fezes/parasitologia , Mucosa Intestinal/parasitologia , Intestino Delgado/imunologia , Intestino Delgado/parasitologia , Músculo Liso/imunologia , Músculo Liso/parasitologia , Contagem de Ovos de Parasitas , Toxocara/imunologia , Toxocara/fisiologiaRESUMO
OBJECTIVE: To determine the frequency and significance of diabetes mellitus (DM)-related autoantibodies in children with autoimmune hepatitis (AIH). RESEARCH DESIGN AND METHODS: Anti-islet cell antibodies (ICA), insulin autoantibodies (IAA), and anti-glutamic acid decarboxylase (GAD65) antibodies were assessed in 28 children (25 female) with AIH before and after 3-9 years of therapy with azathioprine and prednisone. RESULTS: There was biochemical and clinical remission of AIH activity in 76% of the children after 1 year of immunosuppressive therapy. Positive ICA and IAA were found in 60.7% and 18.5% of the patients, decreasing to 38.5% and 12% after 3-9 years of therapy. Anti-GAD autoantibodies were present in only one patient who had Graves' disease, high ICA titer, and developed type 1 DM after 3 years. After 3-9 years of follow up, all had normal fasting glycemia, glycosylated hemoglobin (HbA1c), and, with a single exception, normal responses to oral glucose tolerance testing. No increase in the frequencies of HLA antigens was observed in ICA- and IAA-positive patients compared to antibody-negative patients or a control population. The majority of the patients with HLA-DRB1*03 or DRB1*04, however, were positive for ICA (7/10), and three of them had IAA. The frequency of high risk HLA DQB1*0302 or DQB1*02 alleles was low and similar to control frequencies, indicating low-risk for DM despite the presence of DM-related autoimmunity markers. CONCLUSIONS: AIH in childhood is associated with high frequency of ICA and IAA, with less than expected rates of progression to DM. Immunosuppression reduced ICA and IAA frequency and titers.