04), lower degree of fibrosis (37% × 56% p 0,05) and a trend to a higher frequency of associated autoimmune diseases (39% × 23% p 0,06 Paclitaxel mw ). Anti-SLA was related to lower frequency of biochemical response (48% × 74% p 0,014 ). Anti-LC1 patients presented more frequently with liver failure at presentation (67% × 29% p 0,07) and a trend to higher gammaglobulin levels
(3,9 ±1,4 × 2,8 ±1,2 p 0,06). Comparative analysis of patients with positivity or negativity to anti-Sp100 and anti-gp210 revealed that both were related to older age (45±18 × 32±17 p 0,04 to Sp100 and 42±18 × 32±17 p 0,04 to gp210) and to the diagnosis of OS (56% × 10% p 0,002 to anti-Sp100 and 40% × 9% p 0,005 to anti-gp210). Conclusion: NCAs are promising markers for the evaluation of AIH and OS patients. Besides having a diagnostic role in some cases, they can help in planning strategies for monitoring treatment, contributing for the early identification of more difficult cases and optimization of treatment. Disclosures: check details The following people have nothing to disclose: Elze M. Oliveira, Patricia M.
Oliveira, Ana Cristina A. Feldner, Valéria P. Lanzoni, Renata M. Perez, Ales-sandra Dellavance, Luis Eduardo C. Andrade, Antonio Eduardo B. Silva, Maria Lucia Ferraz INTRODUCTION: Autoimmune hepatitis (AIH) is a disease of unknown aetiology, characterized by a loss of tolerance toward liver antigens resulting in the progressive destruction of the hepatic parenchyma. It is known as a disease mediated by T-cells, with an important
contribution from CD4+ Th1 cells. However, recent studies from small cohorts MCE公司 of AIH patients refractory to conventional treatment have reported successful rescue therapy through B cells depletion with Rituximab, an anti-CD20 monoclonal antibody. AIM: To study the outcome of B-cell depletion in an animal model of AIH and understand the mechanisms underlying the remission.METHODS: A model of AIH in female C57BL/6 mice xenoimmunized with DNA coding for human liver antigens was used. AIH mice were treated with 1 injection of an anti-CD20 monoclonal antibody (Genentech) at the peak of liver inflammation. Serum amino-transferase levels, IP10 expression, circulating B cell levels, autoantibody levels, and total IgG levels were monitored. Liver inflammation and spleen architecture were evaluated. Spleen and liver cell phenotypes were characterized by flow cytometry. B cell function as APCs was analyzed in a lymphoproliferative assay against liver antigens.RESULTS: In the AIH mouse model, B cells were found in liver infiltrates, secreted IFN-γ and TNF-α and proliferated to autoantigen. A single dose of anti-CD20 resulted in more than 95% decrease in circulating B cells (CD45+CD19+) followed by a progressive reconstitution 40 days after injection. A drastic reduction of liver inflammation was observed (p<0.0001), accompanied by a significant reduction of ALT levels (p=0.