Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences

The pathogenesis of autoinimune liver disease and autoimmunity associated w ith chronic viral hepatitis remains poorly understood. One of the major hur dles to a deeper understanding of these pathological processes is the absen ce of clearly defined inductive mechanisms, which, if identified and charac terised, could guide clinical strategies for their prevention or allow ther apeutic intervention. Molecular mimicry leading to crossreactive autoimmune responses has gained strong experimental support in the past decade. A fun damental premise of this hypothesis is the involvement of a mimicking envir onmental trigger. In view of the numerous viral and bacterial agents epidem iologically linked to autoimmune liver diseases, we and others have propose d molecular mimicry to be an important mechanism in these diseases. We also propose similar crossreactive mechanisms to operate in the generation of a utoimmunity in viral hepatitis. This review focuses on molecular mimicry at the level of the B-cell, as few data on T-cell crossreactivity in liver di sease are thus far available.