Anticuerpos antimitocondriales y anticuerpos contra antígenos extraíbles del núcleo en pacientes con cirrosis biliar primaria / Antimitochondrial Antibodies and antibodies against extractable nucleus antigens in patients with primary biliary cirrhosis

Resumen Objetivo: Determinar la frecuencia de anticuerpos antimitocondriales y de anticuerpos contra antígenos extraíbles del núcleo en pacientes con cirrosis biliar primaria. Material y métodos: Estudio de tipo cuantitativo, observacional y transversal, realizado en el Servicio de Inmunología del Hospital Nacional Arzobispo Loayza entre enero 2018 y marzo 2019. Se revisaron las historias clínicas de 30 pacientes con características presuntivas de cirrosis biliar primaria; para la detección de los anticuerpos antinucleares y anticuerpos antimitocondriales se empleó el kit inmunológico en sangre y observación con microscopio de inmunofluorescencia a 40X y para la detección de los anticuerpos contra antígenos extraíbles del núcleo se empleó el método Immunoblot. Resultados: Se estudiaron 30 pacientes con cirrosis biliar primaria, 20 fueron de sexo femenino (66,7%). El patrón de tinción más frecuente fue el citoplasmático moteado reticular en 17(56,7%), seguido del patrón citoplasmático moteado reticular y patrón moteado en 7(23,3%) pacientes, y en menor frecuencia el patrón citoplasmático moteado reticular y patrón centromérico. Nueve (42,9%) pacientes con cirrosis biliar primaria tenían anti-M2. Se demostró mayor frecuencia, 21(70%) de los pacientes con cirrosis biliar primaria tenían anticuerpos antimitocondriales. Conclusiones: Se encontró alta frecuencia de patrón citoplasmático moteado reticular en pacientes con cirrosis biliar primaria, se demostró asociación significativa con los anti-M2 y anticuerpos antimitocondriales.

Summary Objective: To determine the frequency of antimitochondrial antibodies and antibodies against extractable nucleus antigens in patients with primary biliary cirrhosis. Methods : A quantitative, observational and cross-sectional study was carried out at the Immunology Service of the Arzobispo Loayza National Hospital between January 2018 and March 2019. The medical records of 30 patients with presumptive characteristics of primary biliary cirrhosis were reviewed; for the detection of the antinuclear antibodies and antimitochondrial antibodies, the immunological kit was used in blood and observation with a 40X immunofluorescence microscope, and the Immunoblot method was used for the detection of the antibodies against extractable nucleus antigens. Results: Thirty patients with primary biliary cirrhosis disease were studied, 20 were female (66.7%). The most frequent staining pattern was the reticular mottled cytoplasmic in 17 (56.7%), followed by the reticular mottled cytoplasmic pattern and mottled pattern in 7 (23.3%) patients, and less frequently the reticular mottled cytoplasmic pattern and centromeric. Nine (42.9%) patients with primary biliary cirrhosis had anti-M2. In the present investigation, a higher frequency was demonstrated, 21 (70%) of the patients with primary biliary cirrhosis had antimitochondrial antibodies. Conclusions: A high frequency of reticular mottled cytoplasmic pattern was found in patients with primary biliary cirrhosis; a significant association with anti-M2 and antimitochondrial antibodies was demonstrated.

Decreased miR-302e expression in monocytes of patients with primary biliary cirrhosis and its significance / 第二军医大学学报

Objective: To investigate the role of miR-302e in the pathogenesis of primary biliary cirrhosis (PBC). Methods: The relative expression levels of miR-302e in T cells (CD3+), B cells (CD19+) and monocyte (CD14+) of 10 healthy controls and 12 PBC patientswere detected by RT-PCR. The THP-1 cells transfected with miR-302e mimics or inhibitors and the monocytes from PBC patients and healthy controls were treated with 100 ng/ml bacteria lipopolysaccharide (LPS). Twenty- four hours later, the concentrations of IL-6 and TNF-α in the culture medium were measured by ELISA. Results: The monocytes of PBC patients had a significantly lower miR-302e expression compared to those of healthy controls (P<0. 01). miR-302e inhibitors significantly enhanced the production of IL-6 and TNF-α in THP-1 cells exposed to LPS, and miR-302e mimics significantly decreased their production (P<0. 05). When treated with LPS, the monocytes from PBC patients produced significantly more IL-6 and TNF-α compared to those from healthy controls (P < 0. 05). Conclusion: Decreased miR-302e expression in monocytes of PBC patients may enhance IL-6 and TNF-α production and thus participate in the pathogenesis of PBC.

Colangitis esclerosante primaria: [revisión] / Primary sclerosing cholangitis: [review]

La colangitis esclerosante primaria es una patología crónica, poco frecuente, de etiología desconocida, caracterizada por cambios inflamatorios y fibróticos de la vía biliar intra y extrahepática, que produce colestasis, capaz de llevar al desarrollo de una cirrosis biliar secundaria. Su diagnóstico es un reto tanto clínico como radiológico. Históricamente, la prueba de diagnóstica de referencia ha sido la colangiopancreatografía retrógrada endoscópica (CPRE), que es una luminografía y sólo permite la valoración de la vía biliar y deja sin evaluar la pared ductal y el parénquima e hilio hepáticos. Por esta razón la colangiorresonancia (CRM) ha surgido como un método no invasivo, que nos da información adicional a la evaluación de la vía biliar y cuyo rendimiento diagnóstico es comparable a la CPRE. Se revisaron las generalidades clínicas e imaginológicas de la colangitis esclerosante primaria.

Primary sclerosing cholangitis is an uncommon chronic disease of unknown etiology characterized by inflammatory and fibrotic changes of the intra and extrahepatic bile ducts producing cholestasis that can lead to secondary biliary cirrhosis. Historically thegold standard for diagnoses of sclerosing primary cholangitis have been the endoscopic retrograde cholangiography (ERCP), it is known as a luminography due to it only showsthe biliary tract, without evaluation of the hepatic parenchima, ductal wall, hepatic hilium, among others. For this reason the magnetic cholangiography (MRC) has emerged as a new, non-invasive method that give us not only information about the biliary tract but also allows us to evaluate others structures that could be involved in the disease. Furthermore the MRC has a diagnostic performance comparable with the ERCP. We will review the general clinical and imaging features of primary sclerosing cholangitis.

Expression and clinical significance of chemokine receptor in peripheral blood mononuclear cells in patients with primary biliary cirrhosis / 第二军医大学学报

Objective: To investigate the relationship of chemokine receptor with the development and progression of primary biliary cirrhosis (PBC). Methods: Real-time PCR and flow cytometry were used to examine the mRNA and protein expression of chemokine receptor 1 (CCR1), CCR3 and CCR5 in the peripheral blood mononuclear cells (PBMCs) of 60 patients with PBC, 60 patients with hepatitis B-related cirrhosis, and 60 normal controls. Total bilirubin (TBIL) and γ-glutamyltransferase (γ-GT) levels were determined in the patients with PBC and normal controls,and their correlation with chemotactic factors was also analyzed. Results: Both the mRNA and protein expression levels of CCR1, CCR3 and CCR5 in the PBMCs were significantly lower in PBC patients than those in the other two groups (P0.05). CCR3 protein was not linearly correlated with TBIL level (r= -0.173,P>0.05),but was correlated with γ-GT(r= -0.295, P< 0.05). Expression of CCR5 protein was negatively correlated with both TBIL and γ-GT levels(r= -0.531,P<0.01; r=-0.665,P <0.01). Conclusion: CCR1, CCR3 and CCR5 expression is associated with the development and progression of PBC; they may be involved in the regulatory mechanism of PBC,which may cast new lights on the diagnosis and prevention of PBC.

Suplementação com ácido ascórbico tem efeito citoprotetor na cirrose biliar secundária: estudo experimental em ratos jovens / Ascorbic acid supplementation has a cytoprotective effect on secondary biliary cirrhosis: experimental study in young rats

OBJETIVO: Testar se a suplementação com ácido ascórbico tem algum afeito citoprotetor em um modelo de cirrose biliar secundária em ratos jovens. MÉTODOS: Foram estudados 40 ratos Wistar desmamados no 21º dia pós-natal. Cada grupo de 10 foi submetido a um dos seguintes quatro tratamentos, até o 49º dia pós-natal, quando foram submetidos a eutanásia: 1) LC - ligadura dupla e ressecção do ducto biliar comum e administração diária de ácido ascórbico [100 mg/g de peso corporal (pc)]; 2) LA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc); 3) SC - operação simulada e administração diária de ácido ascórbico (100 mg/g pc); 4) SA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc). Os ratos eram pesados diariamente. No 27º dia pós-operatório, eles receberam injeção intraperitoneal de 1,5 mg/g pc de pentobarbital sódico, e o tempo de sono induzido pelo pentobarbital foi medido. Coletou-se sangue para determinação de atividade sérica de alanina aminotransferase e de aspartato aminotransferase, níveis de albumina e globulina séricas, e o fígado foi analisado quanto à conteúdo de água e gordura. Os dados foram submetidos à ANOVA two-way, e comparações pareadas entre grupos foram testadas com o método de SNK. O nível de significância foi estabelecido em 0,05. RESULTADOS: A suplementação com ácido ascórbico atenuou os efeitos da colestase: reduziu o tempo de anestesia pelo pentobarbital, globulina sérica e o conteúdo de gordura no fígado. CONCLUSÕES: Nossos resultados corroboram a hipótese de que a suplementação com ácido ascórbico tem um efeito citoprotetor na cirrose biliar secundária.

OBJECTIVE: To test whether ascorbic acid supplementation has any cytoprotective effect on a model of secondary biliary cirrhosis in young rats. METHODS: We studied 40 Wistar rats weaned at the 21st postnatal day. Each group of 10 was subjected to one of the following four treatments, until 49th postnatal day, when they suffered euthanasia: 1) LC-double ligature and resection of the common bile duct and daily administration of ascorbic acid [100 mg/g of body weight (bw)]; 2) LA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw); 3) SC-sham operation and daily administration of ascorbic acid (100 mg/g bw); 4) SA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw). The rats were weighed daily. On the 27th day after the operation they received an intra-peritoneal injection of 1.5 mg/g bw of sodium pentobarbital, and the pentobarbital sleeping time was measured. Blood was collected for serum alanine aminotransferase and aspartate aminotransferase activity measurements, serum albumin and globulin concentrations, and the liver was assessed for liver water and fat content. Data were submitted to two-way ANOVA and paired comparisons between groups were tested using the SNK method. Significance level was set at 0.05. RESULTS: Ascorbic acid supplementation attenuated the effects of cholestasis: decreased the pentobarbital sleeping time, serum globulin, and the liver fat content. CONCLUSIONS: Our results corroborate the hypothesis that ascorbic acid supplementation has a cytoprotective effect in secondary biliary cirrhosis.

Expression and clinical significance of chemokine receptor in peripheral blood mononuclear cells in patients with primary biliary cirrhosis / 第二军医大学学报

0.05),but was correlated with ?-GT(r=-0.295,P