Members of the glutathione S-transferase gene family are antigens in autoimmune hepatitis

Background & Aims: Autoimmmune hepatitis (AIH), a chronic liver disorder, can be classified into two subtypes on the basis of the specificities of circulating autoantibodies. Type I AIH is defined by antibodies to nuclear and/or smooth muscle antigens (SMA), and type II is characterized by antibodies to cytochrome P450IID6, There is an additional type of AIH characterized by antibodies to a cytosolic soluble liver antigen (SLA), which can occur alone or in combination with antinuclear antibodies and SMA, The aim of this study was to identify the reactive antigen in SLA, a heterogenous cytosolic fraction consisting of at least 100 extremely soluble proteins, Methods: Sera from 31 patients with AIH reacting with SLA and from 30 disease controls were tested, The immunoreactive antigens were determined using immunoprecipitation and immunoblotting after one-and two-dimensional polyacrylamide gel electrophoresis, The antigens were identified by microsequencing of the corresponding protein spots, Results: Twenty-five of 31 anti-SLA-positive sera (80, 7%) reacted with a set of proteins ranging from 25 to 27 kilodaltons that were identified as three subunits of glutathione S-transferases: Ya, Yb-1, and Yc. Conclusions: Glutathione S-transferase subunit proteins represent the major autoantigen in anti-SLA-positive AIH, This new finding permits the establishment of standardized immunoassays for routine diagnosis.