Double Reactivity Against Actin and α-Actinin Defines a Severe Form of Autoimmune Hepatitis Type 1

Anti-filamentous actin antibodies characterize autoimmune hepatitis type 1 (AIH-1). Recently, the binding domain of α-actinin on actin was shown to be a predominant epitope. To test this reactivity, an anti-α-actinin enzyme-linked immunosorbent assay was developed, and positivity confirmed by Western blot. Anti-α-actinin antibody was found in 21/50 (42%) of AIH-1 patients, compared with 52/401 (12.9%) of liver disease control patients, and with 6/200 (6%) of blood donors. Anti-filamentous and anti-α-actinin activities were found specifically together in 66% of anti-filamentous-positive AIH-1 patients. This combination of specificities reflected clinical and histological disease activity, short duration and absence of treatment. Finally, using an actin-α-actinin complex assay, the binding of anti-filamentous actin to α-actinin-binding domain on actin was demonstrated, as well as that of anti-α-actinin on the actin-binding domain of α-actinin. Thus, the frequent combination of anti-filamentous and anti-α-actinin antibodies seems to be the hallmark of activity in AIH-1.