Frequency and significance of anti-glutathione S-transferase autoantibody (anti-GST A1-1) in autoimmune hepatitis

Abstract

Several phase I and phase II multi-drug metabolizing enzymes, such as CYP2D6, 3A4, and UGTA1, were reported to act as immunotargets in a subset of autoimmune hepatitis and hepatic autoimmunity. However, it is uncertain whether glutathione S-transferase (GST) A1-1, one of the phase II multi-drug metabolizing enzymes, is also an immunotarget in autoimmune hepatitis. So, in the present study, we investigated the frequency and significance of anti-GST A1-1 in sera from patients with autoimmune hepatitis. A total of 74 serum samples from patients with autoimmune hepatitis were examined in the present study. As controls, 20 serum samples from patients with primary biliary cirrhosis, 10 serum samples from patients with primary sclerosing cholangitis, 40 serum samples from patients with liver cirrhosis type B and C, 32 serum samples from patients with systemic lupus erythematosus, and 20 serum samples from normal controls were used. Anti-GST A1-1 antibody was determined by immunoblotting using the recombinant full-length GST A1-1 protein as the antigen. The immunofluorescent staining pattern of anti-GST A1-1 was investigated using rat liver and kidney sections. We compared clinicopathologic findings between anti-GST A1-1-positive and -negative autoimmune hepatitis patients. Anti-GST A1-1 was detected in 12 (16%) of 74 patients with autoimmune hepatitis, however, it was not detected in any control serum samples except for two patients with primary biliary cirrhosis. The immunofluorescence staining pattern of anti-GST A1-1 was found to be unique and different from those of anti-mitochondrial antibody or anti-liver-kidney microsome type 1 antibody. Anti-GST A1-1 coexisted with other autoantibodies such as anti-nuclear or anti-smooth muscle antibodies, but did not coexist with anti-soluble liver antigen/liver pancreas. Anti-GST A1-1-positive autoimmune hepatitis patients had severe clinical features and a poor prognosis compared with anti-GST A1-1-negative patients. These findings suggested that despite the low frequency, anti-GST A1-1 might be the marker of an early progression in autoimmune hepatitis.