Hepatopatías autoinmunes. Hallazgos clínicos y de laboratorio en pacientes de un hospital de referencia nacional / Autoimmune liver diseases. Clinical and laboratory findings in patients in a national reference hospital

Introducción. Las enfermedades autoinmunes del hígado son un grupo de patologías caracterizadas por una respuesta autoinmune contra los hepatocitos y/o el epitelio biliar. Sus manifestaciones clínicas son variadas, con alteraciones en las pruebas de función hepática y presencia de autoanticuerpos. Metodología. Estudio observacional descriptivo con 101 pacientes atendidos en el Hospital Universitario de La Samaritana de Bogotá D.C., entre enero a diciembre de 2019, con los diagnósticos de hepatitis autoinmune, colangitis biliar primaria, colangitis esclerosante primaria y síndrome de sobreposición. Se evaluaron los parámetros clínicos y de laboratorio, con el fin de caracterizar su frecuencia en estas patologías, debido a la importancia de un diagnóstico precoz. Resultados. Se encontraron 54 casos de hepatitis autoinmune, 19 casos de colangitis biliar primaria, 4 casos de colangitis esclerosante primaria y 24 casos de síndrome de sobreposición. El 81% fueron mujeres y la edad promedio fue de 55 años. El 39% de los pacientes tenían cirrosis. En general, los resultados se ajustaron a lo descrito internacionalmente, como es el predominio en mujeres y la comorbilidad autoinmune. Conclusión. Los hallazgos indican que cualquier alteración del perfil bioquímico hepático debe ser considerado, y se debe descartar la presencia de hepatopatías autoinmunes para diagnosticarlas de manera precoz, evitando que lleguen a cirrosis y sus complicaciones, con la necesidad de un trasplante hepático como única alternativa terapéutica.

Introduction. Autoimmune liver diseases are a group of pathologies characterized by an autoimmune response against hepatocytes and/or the biliary epithelium. Their clinical manifestations are varied, with alterations in liver function tests and the presence of autoantibodies. Methodology. Descriptive study with 101 patients who attended at the Hospital Universitario de La Samaritana in Bogota D.C., between January and December 2019, with the diagnoses of autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis and overlap syndrome. Clinical and laboratory parameters were evaluated in order to characterize their frequency in these pathologies, due to the importance of an early diagnosis. Results. There were 54 cases of autoimmune hepatitis, 19 cases of primary biliary cholangitis, 4 cases of primary sclerosing cholangitis, and 24 cases of overlap syndrome. Of all patients, 81% were women, the average age was 55 years, and 39% had cirrhosis. In general, the findings were consistent with what has been described worldwide, such as a higher prevalence in women and autoimmune comorbidity. Conclusion. The findings indicate that any alteration in the liver biochemical profile should be considered to rule out an autoimmune liver disease for an early diagnosis, avoiding the possibility of cirrhosis and its complications, with the need for a liver transplant as the only therapeutic alternative.

Diagnóstico de hepatitis autoinmune / Diagnosis of autoimmune hepatitis

La hepatitis autoinmune es una enfermedad inflamatoria del hígado de etiología desconocida, que se caracteriza por la presencia de autoanticuerpos y niveles altos de globulinas séricas. Afecta a ambos sexos, a todos los grupos de edad, y se ha descrito en todas las razas. Tiene una amplia variedad de presentación clínica, lo que la convierte en un reto diagnóstico para el médico. La forma de presentación más común es la hepatitis aguda; sin embargo, un porcentaje no despreciable de pacientes es asintomático y hasta el 40% de los casos tiene cirrosis al momento del diagnóstico. El diagnóstico se basa en: 1) la medición de autoanticuerpos, como los antinucleares (ANA), los antimúsculo liso (ASMA), y los antimicrosomales de hígado y riñón (anti-LKM-1); 2) la detección de niveles séricos elevados de globulinas (especialmente IgG); 3) descartar otras etiologías de hepatitis crónica; y, 4) los hallazgos histológicos, los cuales además de confirmar el diagnóstico, ayudan a establecer la severidad. Se han desarrollado escalas y puntajes diagnósticos que permiten una mejor aproximación a dicha patología sin reemplazar el juicio del médico, por lo que deben ser interpretados bajo un adecuado contexto clínico. Un diagnóstico apropiado puede permitir el inicio oportuno de tratamiento con el fin de disminuir la progresión y el desarrollo de complicaciones.

Autoimmune hepatitis is an inflammatory disease of the liver of unknown etiology. It is characterized by the presence of autoantibodies and elevated levels of serum globulins. It affects both genders, all age groups and has been described in all races. It has a wide variety of clinical manifestations, so it remains a diagnostic challenge for physicians. The most common form of manifestation is acute hepatitis, however a non-negligible percentage of patients is asymptomatic, and up to 40% of cases have cirrhosis at the time of diagnosis. The diagnosis is based on: 1) measurement of autoantibodies, such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), and liver/kidney microsomal type 1 antibodies (anti-LKM-1); 2) detection of elevated serum levels of globulins (especially IgG); 3) exclusion of other causes of chronic hepatitis; and, 4) histological findings, which also confirm the diagnosis and help determine its severity. Diagnostic scales and scores have been developed to allow a better approach to this pathology without replacing the clinical judgment, so they must be interpreted under an adequate clinical context. A proper diagnosis can allow a timely initiation of treatment in order to decrease the progression and the development of complications.

Extract of Ascaris suum induces TGF-ß and early production of IgG1 in experimental autoimmune hepatitis / Extrato de Ascaris suum induz TGF-ß e produção precoce de IgG1 na hepatite autoimune experimental

Abstract In experimental autoimmune hepatitis (EAH) of Th1 profile, an extract of adult Ascaris suum worms (ASC) was previously found to deviate the immune response to a Th2/IL-10 pattern. Here, the effects of treatment with ASC on production of TGF-β and the anti-Ascaris isotypes IgG1 and IgG2a in EAH were evaluated. EAH was induced in BALB/c mice, intravenously with concanavalin A. Two hours later, these animals received ASC (EAH+ASC group) or PBS vehicle (EAH group). IgG1 and IgG2a were evaluated 8 h, 24 h and 7 d after induction. TGF-β was measured in a splenocyte culture at this last time. The isotype levels in the EAH group were low throughout the kinetics. In the EAH+ASC group, there was significant production of IgG1 at 24 h and 7 d, but of IgG2a only at 7 d. There was statistically greater production of TGF-β in the EAH+ASC group. The higher levels of IgG1 and TGF-β in this group suggest that an additional Th1 response control route exists in EAH, which needs to be investigated.

Resumo Na hepatite autoimune experimental (HAE) de perfil Th1, o extrato de vermes adultos Ascaris suum (ASC) desviou a resposta imune para um padrão Th2/IL-10. Neste trabalho, foram avaliados os efeitos do tratamento com ASC na produção TGF-β e dos isótipos de IgG1 e IgG2a anti-Ascaris na HAE. Esta foi induzida em camundongos BALB/c intravenosamente com Concanavalina A. Após duas horas, os animais receberam ASC (grupo HAE+ASC) ou veículo PBS (grupo HAE). IgG1 e IgG2a foram avaliados em 8 horas, 24 horas e 7 dias após indução. TGF-β foi mensurado em cultura de esplenócitos nesse último tempo. Os níveis dos isótipos no grupo HAE foram baixos durante toda a cinética. No grupo HAE+ASC, houve produção significativa de IgG1 em 24 horas e 7 dias, mas somente em 7 dias para IgG2a. A produção de TGF-β foi estatisticamente maior no grupo HAE+ASC. Níveis mais altos de IgG1 e TGF-β nesse grupo sugerem uma via adicional de controle da resposta Th1 na HAE que precisa ser investigada.

Evaluation of frequency of autoimmune hepatitis autoantibodies in children with type 1 diabetes / Frecuencia de anticuerpos de hepatitis autoinmune en niños con diabetes tipo I

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.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes / Hepatite autoimune em 828 crianças e adolescentes brasileiros: achados clínicos e laboratoriais, perfil histológico, tratamentos e resultados

Abstract Objective: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. Methods: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

Resumo Objetivo: Este estudo com acompanhamento de longo prazo visou a avaliar o quadro clínico, os achados laboratoriais, o perfil histológico, os tratamentos e os resultados de crianças e adolescentes com hepatite autoimune. Métodos: Foram analisados os prontuários médicos de 828 crianças e adolescentes com HAI. Foi usado um questionário para coletar os dados anônimos sobre o quadro clínico, os achados bioquímicos e histológicos e os tratamentos. Resultados: De todos os pacientes, 89,6% tinham hepatite autoimune-1 e 10,4% hepatite autoimune-2. O sexo feminino foi predominante nos dois grupos. A idade média no início dos sintomas foi 111,5 (6; 210) e 53,5 (8; 165) meses nos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. Foi observado início clínico agudo em 56,1% e 58,8% e sintomas insidiosos em 43,9% e 41,2% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. A probabilidade de insuficiência hepática foi 1,6 vezes maior para hepatite autoimune-2; 3,6% e 10,6% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente, apresentaram insuficiência hepática fulminante; o risco foi 3,1 vezes maior para hepatite autoimune-2. Os níveis de gamaglobulina e imunoglobulina G foram significativamente maiores nos pacientes com hepatite autoimune-1, ao passo que os níveis de imunoglobulina A e C3 foram menores em pacientes com hepatite autoimune-2; 22,4% dos pacientes apresentaram cirrose e a remissão bioquímica foi atingida em 76,2%. A taxa de sobrevida atuarial foi de 93,0%. Um total de 4,6% pacientes foram submetidos a transplante de fígado e 6,9% morreram (hepatite autoimune-1: 7,5%; hepatite autoimune-2: 2,4%). Conclusões: Nesta grande série clínica de crianças e adolescentes brasileiros, a hepatite autoimune-1 foi mais frequente e os pacientes com hepatite autoimune-2 mostraram maiores taxas de remissão da doença com respostas mais rápidas aos tratamentos. Os pacientes com hepatite autoimune-1 apresentaram maior risco de óbito.

Daño hepatocelular, proteinuria y autoinmunidad: ¿enfermedad multisistémica o coincidencia de enfermedades? Caso clínico / Hepatocellular damage, proteinuria and autoimmunity: multisystemic disorder or coexistence of diseases?

We report a 19 years old male presenting with knee pain, elevated liver enzymes and proteinuria. Further investigation found positive antinuclear and anti-smooth muscle antibodies and a liver biopsy revealed the presence of an autoimmune hepatitis. Treatment with corticosteroids and azathioprine was started, resulting in normalization of liver enzymes but proteinuria persisted and a kidney biopsy disclosed a focal segmental glomerulosclerosis. The use of lisinopril resulted in a significative reduction of proteinuria and, after 30 months of follow up, he continues with azathioprine, lisinopril and a low prednisone dose without evidence of liver or kidney disease activity.

Impaired T cell-mediated hepatitis in peroxisome proliferator activated receptor alpha (PPARα)-deficient mice

Abstract Background Peroxisome proliferator activated receptor alpha (PPARα), a regulator of enzymes involved in β oxidation, has been reported to influence lymphocyte activation. The purpose of this study was to determine whether PPARα plays a role in T cell-mediated hepatitis induced by Concanavalin A (ConA). Methods Wild type (wt) or PPARα-deficient (PPARα−/−) mice were treated with ConA (15 mg/kg) by intravenous injection 0, 10 or 24 h prior to sacrifice and serum and tissue collection for analysis of tissue injury, cytokine response, T cell activation and characterization. Results Ten and 24 h following ConA administration, wt mice had significant liver injury as demonstrated by serum transaminase levels, inflammatory cell infiltrate, hepatocyte apoptosis, and expression of several cytokines including interleukin 4 (IL4) and interferon gamma (IFNγ). In contrast, PPARα−/− mice were protected from ConA-induced liver injury with significant reductions in serum enzyme release, greatly reduced inflammatory cell infiltrate, hepatocellular apoptosis, and IFNγ expression, despite having similar levels of hepatic T cell activation and IL4 expression. This resistance to liver injury was correlated with reduced numbers of hepatic natural killer T (NKT) cells and their in vivo responsiveness to alpha-galactosylceramide. Interestingly, adoptive transfer of either wt or PPARα−/− splenocytes reconstituted ConA liver injury and cytokine production in lymphocyte-deficient, severe combined immunodeficient mice implicating PPARα within the liver, possibly through support of IL15 expression and/or suppression of IL12 production and not the lymphocyte as the key regulator of T cell activity and ConA-induced liver injury. Conclusion Taken together, these data suggest that PPARα within the liver plays an important role in ConA-mediated liver injury through regulation of NKT cell recruitment and/or survival.

Hepatitis autoinmune en la edad pediátrica / Autoimmune hepatitis in the pediatric age

Resumen: En pediatría, la hepatitis autoinmune y la colangitis esclerosante son patologías de afección hepática cuyo mecanismo de daño es inmunológico. La hepatitis autoinmune es una enfermedad de etiología desconocida, caracterizada por hepatitis de interfase, hipergammaglobulinemia, autoanticuerpos circulantes y una respuesta favorable a la inmunosupresión. Es una enfermedad eminentemente pediátrica, con una afección prevalente hacia mujeres jóvenes. La terapia debe ser instituida con prontitud para prevenir el deterioro rápido, promover la remisión de la enfermedad y la supervivencia a largo plazo. La falta persistente de respuesta o la falta de adherencia al tratamiento dan como resultado una enfermedad hepática terminal. Los pacientes que desarrollan esta patología, y aquellos con insuficiencia hepática fulminante en el momento del diagnóstico, requerirán trasplante hepático.

Abstract: In pediatrics, autoimmune hepatitis and sclerosing cholangitis are liver disorders with an immunological damage mechanism. Autoimmune hepatitis is a disease of unknown etiology characterized by interface hepatitis, hypergammaglobulinemia, circulating autoantibodies and a favorable response to immunosuppression. It is an eminently pediatric disease with a prevalent condition in young women. Therapy should be instituted promptly to prevent rapid deterioration, promote remission of disease and long-term survival. The persistent lack of response or lack of adherence to treatment results in terminal liver failure; these patients, and those with fulminant hepatic insufficiency at the time of diagnosis, will require liver transplantation.

Acute Hepatitis E Mimicking a Flare of Disease in a Patient with Chronic Autoimmune Hepatitis

Abstract: Acute hepatitis E is becoming increasingly recognised in Europe with up to 40% of the population in Southern France being exposed to the virus, which is harboured in pigs. Patients with known liver disease may present with acute hepatitis E and present a diagnostic challenge. For example patients with autoimmune hepatitis (AIH) who are immunosuppressed and contract hepatitis E may be at increased risk of developing chronicity due to concurrent immunosuppression. Importantly, the diagnosis may be missed with the infection misdiagnosed as an autoimmune flare, and immunosuppression increased by the attending physician, thus enhancing the risk of chronicity of infection leading to progressive liver injury in immunocompromised patients. We report a case of acute hepatitis E in a patient with AIH and discuss the features that helped us differentiating it from an autoimmune flare.

Hepatitis autoinmune en niños: diagnostico / Autoimmune hepatitis in children: diagnosis

El diagnóstico de la hepatitis autoinmune (HAI), se basa en una serie de criterios definidos por elGrupo Internacional de HAI (IAIHG) que permite clasificarla como HAI probable o definitiva. Un criterio clave para el diagnóstico de la HAI es la detección de ANA, SMA, y anti- LKM-1 por inmunofluorescencia indirecta. Otros anticuerpos menos frecuentes probados, pero de importancia diagnóstica en HAI pediátrica incluyen los anticuerpos tipo: citosol 1 hígado (LC-1), anti- citoplasma de los neutrófilos (ANCA) y el antígeno soluble hepático (SLA). La Ig G está usualmente elevada en ambos tipos de HAI, cerca del 15% de niños con HAI I y el 25% de niños con HAI tipo II tienen valores normales. La biopsia hepática es necesaria para establecer el diagnóstico de HAI.

The diagnosis of autoimmune hepatitis (HAI), is based on a set of criteria defined by the International HAI Group (IAIHG) that allows classified as a probable or definite HAI. A key criterion for the diagnosis of HAI is the detection of ANA, SMA, and anti-LKM-1 by indirectimmunofluorescence. Other less common antibodies tested, but important diagnostic tool in pediatric HAI include antibodies such as: liver cytosol 1 (LC-1), anti-neutrophil cytoplasmic (ANCA) and soluble liver antigen (SLA). The Ig G is usually high in both types of HAI, about 15% of children with HAI I and 25% of children with HAI type II are normal. Liver biopsy is necessary to establish the diagnosis of HAI.

Recurrencia de la enfermedad hepática primaria después del trasplante hepático / Liver disease recurrence after liver transplantation

Liver transplantation has become a standard option in the management of patients with end-stage liver disease. It is now evident that the most common etiology of long-term graft dysfunction is the recurrence of the primary liver disease. Autoimmune liver disorders such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis recur between 15 to 30 percent of the graft recipients. The clinical expression of this recurrence tends to be milder; the diagnosis is only established in many patients by fndings in the liver biopsy. This milder clinical expression may be due to the use of immunosuppressive therapy for the prevention of organ rejection and it may also be modulating immune mechanisms that underlie these conditions. The recurrence of hepatitis C virus infection is characterized by an accelerated progression towards cirrhosis and hepatic failure due to the lack of an effective immunoprophylaxis program and an effective antiviral therapy. The recurrence of hepatitis B is uncommon due to the availability on an effective immunoprophylaxis program with effective antiviral agents. The familial amyloidotic polyneuropathy is a genetic condition residing in the hepatocyte that produces a mutation of transthyretin; this abnormal protein is deposited in peripheral nerves, gastrointestinal tract, heart, and kidneys. The liver from these patients, apart from producing this abnormal protein, is otherwise normal, and has been used as an organ for recipients in dire need of a liver transplant, such as patients with hepatocellular carcinoma. This approach is known as “domino” liver transplantation. As these recipients are followed long term, they may develop de novo amyloidosis. In summary, the underlying liver condition that led to endstage liver disease and liver transplantation may recur after liver transplantation. The clinical expression of the recurrence of the hepatic disease is modulated by the immunosuppression...

Estudo de prevalência de auto-anticorpos não órgão específicos em população rural do nordeste brasileiro (Cavunge-Ba) / Study of the prevalence of autoantibodies not specific national rural population of Northeast Brazil (Cavunge-Ba)

Os auto-anticorpos hepáticos (AAH), incluindo os anticorpos antinúcleo (ANA), antimúsculo liso (SMA), antimicrossoma de fígado e rim do tipo 1 (anti-M1), anticitosol hepático do tipo 1 (anti-LC1) e antimitocôndria (AMA), podem ser encontrados em 1 por cento a 43 por cento dos indivíduos saudáveis, sendo considerados auto-anticorpos naturais. Por outro lado, são também considerados marcadores de enfermidades auto-imunes, particularmente hepatite auto-imune (HAI) e cirrose biliar primária (CBP), duas doenças auto-imunes do fígado de prevalência ainda desconhecida na população brasileira. Com o intuito de avaliar a freqüência de AAH na população normal e sua correlação com estado de doença e de investigar a prevalência de HAI e CBP no Brasil, foram coletadas amostras de soro de 725 indivíduos, aleatoriamente selecionados, residentes no povoado de Cavunge para realização de AAH por imunofluorescência indireta (IFI), empregando cortes de roedores, fibroblastos e células Hep-2. Os resultados foram comparados com dados demográficos e marcadores sorológicos de infecção por vírus A, B e C. Positividade para AAH foi considerada na presença de titulação igualou superior a 1:40, sendo considerada clinicamente relevante titulação igualou superior a 1:80. Cento e um indivíduos (14 por cento) apresentaram reatividade para AAH, a maioria com títulos de 1:40, sendo observada positividade para SMA, ANA e AMA em respectivamente 10 por cento, 4 por cento e 0,1 por cento dos indivíduos. Não foi encontrada reatividade para anti-LKM 1 e anti-LC 1. Os principais padrões de IFI para SMA e ANA foram, respectivamente, vaso e glomérulo I e nuclear pontilhado grosso. Apenas um indivíduo com SMA exibiu reatividade para anti-microfilamento em baixo título, não sendo observado...

autoimmune diseases manifested by production of autoantibodies: the autoantigens identified by random peptide library

Phage-displayed random peptide libraries [RPL] provide a powerful technique for identification, structural and functional analysis of ligands for many different target molecules, including, antibodies, receptors or other proteins. This strategy has been verified to be an effective tool for research in immunology and successfully has been used to determine the target sequence for monoclonal and polyclonal antibodies. The peptide library approach provides great promise for characterization of ligands with no prior information concerning antibody specificity. This would allow the recognition of candidate antigens involved in initiation or perpetuation of autoimmune diseases. This technology also offers the potential for new therapeutic opportunities, production of diagnostic reagents, or even development of effective new vaccines. This review focuses on studies regarding the identification of autoantigens recognized by antibodies in autoimmune diseases using phage-display peptide libraries

comparison of the prevalence of anti-liver/kidney microsome antibody type-1[LKM-1] in individuals with chronic hepatitis C and those with autoimmune hepatitis

Autoantibodies are frequently found in patients with chronic hepatitis C, which suggests that HCV elicit an immune response in the host]. The relationship of type-2 AIH to chronic hepatitis C [HCV] is an interesting and as yet unresolved problem. Importantly, antibodies to liver/kidney microsome type- I [LKMI], the serologic marker of type 2-AIH, have been recognized in serum of some patients with chronic hepatitis C. Anti-liver kidney microsome type 1 [LKM-1] autoantibodies were studied by indirect immuno florescence assay [lIF] and confirmed by immunoblot in the serum of 73 Iraqi patients with autoimmune hepatitis [AIH] in comparison with 50 patients control [HCV infection] and 50 healthy individuals. anti-LKZM 1 with high titers [>/= 1/160] present in serum of al/patients with AIH-2, whereas they present in titer [

Serological diagnosis of autoimmune hepatobiliary diseases

Autoimmune hepatobiliary diseases AIHBD comprise autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis and the overlap syndromes. Early diagnosis and treatment of AIHBD are essential for the prevention of the high morbidity, and mortality, that is, otherwise, associated with untreated patients. Screening for AIHBD relies heavily on the use of serological tests for the detection of serum autoantibodies that associate with the diseases. Understanding these tests, and the results produced, is important for the efficient diagnosis/exclusion of these diseases. In this review, we discuss the various tests available in the clinical immunology laboratory for screening of AIHBD and comment on the significance of the results produced by each test. We hope that this review will highlight this group of autoimmune diseases and lead to more efficient and earlier diagnosis, and treatment, of patients with AIHBD

Anticuerpos anti LKM-1 y crioglobulinemia en hepatitis crónica autoinmune y por virus C de la hepatitis / Anti LKM-1 and cryoglobulinemia in autoimmune and virus C associated chronic hepatitis

Background: Anti liver kidney microsome antibodies (LKM-1) have been recently incorporated to the study and classification of chronic autoimmune hepatitis (HC-A1). The presence of anti LKM-1 antibodies and essential cryoglobulinemia is frequent in virus C associated chronic hepatitis (HC-VC). Aim: To study the frequency of anti LKM-1 antibodies and cryoglobulin levels in patients with HC-AI, HC-VC and cryptogenic cirrhosis. Patients and methods: Forty two patients were studied. Nineteen adult women with classic HC-AI with positive antinuclear or anti smooth muscle antibodies. Five patients of less than 20 years old with HC-AI and negative antinuclear and anti smooth muscle antibodies. Ten adult women with cryptogenic cirrhosis, 4 women and 4 men with HC-VC. Serum samples were obtained at 37­C. Antinuclear, anti smooth muscle and anti LKM-1 antibodies were measured by indirect immunofluorescence using Hep-2 cells and rat tissue slices as substrates. Cryoglobulins were determined by the traditional method and cryocrit. Results: All studied patients were anti LKM-1 negative. All had significant circulating cryoglobulin levels. Conclusions: In this sample of patients with HC-AI or HC-VC, anti LKM-1 antibodies were not detected but all had cryoglobulinemia

Immunohistopathological reactions for liver-specific membrane lipo-protein in experimental autoimmune hepatitis.

Antibody to the hepatocyte membrane protein, was induced in inbred strain C57BL/6 and C3H mice by immunisation with 100,000 g supernatant of syngeneic liver homogenate in CFA. Three weekly intraperitoneal injection of 200 ul of liver homogenate with CFA for continuous 4 weeks gave the best possible result. Histopathological changes were characterised mainly by perivascular inflammatory infiltrates and hepatocyte necrosis which mimicked human autoimmune hepatitis. In one of the immunological parameters, antibody to hepatocyte membrane protein (LSP) has been demonstrate by ouchterlony method in the test serum of those animals, who had received weekly doses of liver antigen. Thus in experimental autoimmune liver disease, semi-purified syngeneic liver fluid (S-100) leads to hepatic destruction and to an inflammatory process with several features in common with human chronic aggressive hepatitis. The presence of antibody against syngeneic liver antigen (S-100) in the test sera emphasizes that hepatocyte membrane protein does have an important role in liver tissue pathogenesis and disease process in experimental model. In this study we tried to prove that hepatocyte membrane protein may act as a target antigen in developing experimental autoimmune hepatitis.

Anticuerpos anti-citoplasma de neutrófilos: aspectos bioquímicos y metodológicos, importancia en diferentes patologías / Antineutrophil cytoplasmic antibodies: biochemical and methodological aspects, their importance in diferents pathologies

Los anticuerpos anticitoplasma de neutrófilos, ANCA, se encuentran involucrados en la patogénesis de las diferentes formas de las vasculitis inmunes. Su descubrimiento y posterior estudio ha permitido su utilización como elemento de ayuda diagnóstica y de seguimiento en enfermedades tales como la granulomatosis de Wegener, panarteritis microscópica y glomerulonefritis cresenticas necrotizantes. El objetivo de esta revisión es tratar de comprender las diferentes formas de vasculitis y así orientarse con respecto al diagnóstico de las mismas. La técnica de inmunofluorescencia indirecta (IFI) que hasta el momento es la única normatizada, sigue siendo una herramienta fundamental para la detección de ANCA dada su elevada especificidad; pero no debe olvidarse que posee como interferentes a los anticuerpos antinucleares (ANA). Se desarrolló un absorvente a partir de un extracto nucleoproteico de timo vacuno que permite eliminar la interferencia que producen los ANA cuando están presente en una muestra donde se quiere determinar ANCA. De esta manera se logró optimizar la IFI-ANCA, lo cual quedó demostrado que los resultados obtenidos cuando se utilizó esta técnica en conjunto con ELISA antígeno específico, LIA blot antígeno específico y Dot blot gránulos Ó desarrollados. Resultados preexistentes en relación con los ANCA y colangenopatías como el lupus eritematoso sistémico (LES) pediátrico y la artritis reumatoidea (AR) mostraban resultados dispares entre diferentes autores, lo que generó la inquietud de estudiar la seroprevalencia en estas enfermedades y su importancia clínica. Se demostró relación entre ANCA e insuficiencia renal en LES pediátrico, no así en AR. Se generó la hipótesis que la presencia de ANCA sea un epifenómeno derivado de la respuesta inflamatoria. También se pudo demostrar la presenciade ANCA en pacientes con glomerulopatías sin evidencias clínicas ni anatomopatológicas de vasculitis como son las glomerulopatías: de la diabetes, IgA, membranoproliferativas, mesangial, membranosa, nefroesclerosis, esclerosis focal y segmentaria, todas ellas asociadas a microhematuria y/o proteinuria en diferentes grados. Finalmente la revisión de este tema y en particular el desarrollo y optimización de los métodos de detección ha permitido ampliar y profundizar el campo de estudio en relación con los ANCA arribando a las conclusiones aquí expresadas

Associação dos antígenos HLA-DR e DQ com a hepatite auto-imune tipos 1 e 2 / Association of HLA-DR and DQ with autoimmune hepatitis types 1 and 2

A susceptibilidade genética à hepatite auto-imune tipo 1 (HAI-1) foi associada aos antígenos de HLA-DR3, DR52 e DR4 em pacientes europeus e norte­ americanos, ao HLA-DR4 no Japão e aos HLA-DR4 e DR13 na América Latina. A predisposição à HAI-1 não foi estudada em outros grupos étnicos e poucos estudos avaliaram pacientes com hepatite auto-imune tipo 2 (HAI-2). O objetivo deste estudo foi investigar a associação dos HLA-DR e DQ em pacientes brasileiros com HAI-1 e HAI-2 e comparar as freqüências desses antígenos com parâmetros clínicos e laboratoriais da doença e com a resposta ao tratamento. A determinação de HLA-DRB e DQB1 foi realizada por PCR-SSP em 143 pacientes e em 126 indivíduos saudáveis. Cento e quinze pacientes apresentaram HAI-1 com reatividade para anticorpo anti-actina (AAA) elou anticorpo antinúcleo (AAN)...