MEMBERS OF THE GLUTATHIONE-S-TRANSFERASE GENE FAMILY ARE ANTIGENS IN AUTOIMMUNE HEPATITIS

Background & Aims: Autoimmmune hepatitis (AIH), a chronic liver disord er, can be classified into two subtypes on the basis of the specificit ies of circulating autoantibodies. Type I AIH is defined by antibodies to nuclear and/or smooth muscle antigens (SMA), and type II is charac terized by antibodies to cytochrome P450IID6, There is an additional t ype of AIH characterized by antibodies to a cytosolic soluble liver an tigen (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 le ast 100 extremely soluble proteins, Methods: Sera from 31 patients wit h 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 electr ophoresis, The antigens were identified by microsequencing of the corr esponding protein spots, Results: Twenty-five of 31 anti-SLA-positive sera (80, 7%) reacted with a set of proteins ranging from 25 to 27 kil odaltons that were identified as three subunits of glutathione S-trans ferases: Ya, Yb-1, and Yc. Conclusions: Glutathione S-transferase subu nit proteins represent the major autoantigen in anti-SLA-positive AIH, This new finding permits the establishment of standardized immunoassa ys for routine diagnosis.