Development of autoimmune hepatitis-like disease in mice infected with mouse

J. L. APARICIO, C. PEÑA AND L. A. RETEGUI

INTERNATIONAL IMMUNOPHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2011 p. 1591 - 1598

1567-5769

Mouse hepatitis virus A59 (MHV A59) induces autoantibodies (autoAb) to fumarylacetoacetate hydrolase (FAH), a soluble cytosolic enzyme present in the liver and kidneys, in various mouse strains. Thus, the aim of this work was to amplify and diversify the autoimmune response restricted to FAH through the use of the exogenous adjuvant called PADRE. Accordingly, C57BL/6 mice were chosen, because these animals respond to PADRE better than other mouse strains. Results presented herein indicate that, surprisingly, C57BL/6 mice are much more susceptible to infection with MHV than other mouse strains. These animals developed signs of autoimmune hepatitis-like disease (AIH), including transient hypergammaglobulinemia, elevated transaminases, autoAb directed against different liver proteins and hepatic cellular infiltrates, indicating that a new model of experimental AIH could be generated by a viral inoculation. Furthermore, PADRE administration amplified the effect of the viral infection, extending the duration of hypergammaglobulinemia and increasing the binding of autoAb as well as the extent of hepatic lesions. Since plasmatic uric acid and high-mobility group box protein 1 (HGMB1) concentrations augmented in MHV- and/or PADRE-treated mice, it is suggested that both alarmins were probably involved in the spreading of the immune response induced by the viral infection and the adjuvant administration.