Remission with ursodeoxycholic acid of type 1 autoimmune hepatitis resistant to azathioprine and steroids.

Combination therapy with steroids and azathioprine is the reference treatment for autoimmune hepatitis, but potential adverse effects are numerous and intolerance can occur. We report a patient with a well-documented type 1 autoimmune hepatitis intolerant to corticosteroids and azathioprine therapy, in whom eight years of ursodeoxycholic acid monotherapy was associated with biochemical and histological remission.

Concomitant early appearance of anti-ribonucleoprotein and anti-nucleosome antibodies in lupus prone mice.

OBJECTIVE: To gain insights on initial stages of the autoimmune response in lupus prone mice taking advantage of new sensitive and quantitative techniques for the detection of autoantibodies specific for RNA- (ribonucleoproteins) and DNA-protein (chromatin) complexes. METHODS: DNA and nucleosome antibodies were detected by ELISA, antibodies to SmB, U1A-RNP, Ro52, Ro60 and La by a new radioligand assay, using de novo synthesized radio-labeled antigens. RESULTS: Analysis of anti-chromatin (including anti-nucleosome, anti-dsDNA and anti-histone antibodies) and of anti-snRNP antibodies (including anti-U1A-RNP, anti-SmB, anti-Ro52, anti-Ro60, anti-La antibodies) was performed in sequential sera from B/W, MRL+/+, MRL Yaa and MRL lpr/lpr mice. In a cohort of 105 MRL+/+ mice of different ages, 59, 51, and 57 mice were positive for anti-nucleosome, anti-SmB and anti-U1A-RNP, respectively. None of them was positive for anti-dsDNA. Importantly, antibody positivities were not randomly distributed but were significantly clustered in individual mice. Appearance of DNA- and RNA-protein complex antibodies started at approximately 18-20 weeks of age, preceding that of the anti-dsDNA (or anti-histone) antibodies that only started at 30-32 weeks. Anti-nucleosome, anti-SmB and anti-U1A-RNP antibody responses did not display any cross-reactivity as demonstrated by inhibition and adsorption experiments. CONCLUSION: These data indicate that anti-nucleosome and anti-snRNP antibodies appear early and concomitantly in lupus prone mice even though they do not share any cross-reactivity. These results fit with the assumption that their production is triggered by tightly physically associated nucleosomes and snRNP autoantigens contained in the same apoptotic bodies.

Detection of neutralizing antibodies to hepatitis C virus using a biliary cell infection model.

The identification and characterization of neutralizing anti-hepatitis C virus (HCV) antibodies may have a major impact on understanding HCV pathogenesis. However, to date, their detection has only been based on the inhibition of either the E2 envelope protein or HCV virions binding to different target cells. The permissiveness of primary biliary cells for HCV infection has been demonstrated previously. In the present report, infection of biliary cells was demonstrated further by combining PCR and immunohistochemical detection of the HCV core protein. This study demonstrates, using both serum and purified IgG, the presence of neutralizing anti-HCV antibodies in the serum of patients showing long-term response to antiviral therapy. Overall, the usefulness of the primary biliary cell infection model to investigate anti-HCV neutralization is shown.