Gastroenterology

Gastroenterology

Volume 114, Issue 2, February 1998, Pages 329-335
Gastroenterology

Liver, Pancreas, and Biliary Tract
Members of the glutathione S-transferase gene family are antigens in autoimmune hepatitis,☆☆

https://doi.org/10.1016/S0016-5085(98)70485-8Get rights and content

Abstract

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, Yb1, 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.

GASTROENTEROLOGY 1998;114:329-335

Section snippets

Patients

Sera were obtained from 31 untreated patients with AIH who were seropositive for anti-SLA antibodies. Testing for anti-SLA followed the method described by Manns et al.7 Twenty-five of the patients were women (81%) with a mean age of 40 years (range, 7–63 years), and 7 (23%) had associated cirrhosis at the initial evaluation. Of the serum samples of 31 patients, 12 reacted solely with SLA. Of the remaining 19 sera, 10 were also positive for ANA, 4 reacted with SMA, and 5 had both ANA and SMA.

Results

Immunoblotting screening tests performed with 31 anti-SLA–positive sera and rat liver cytosol as antigen showed positivity for several cytosol proteins. To characterize the target antigen(s), we performed three different approaches. We first allowed immune complexes to form by immunodiffusion using rat liver cytosol as antigen source. The immune complexes were isolated and then carefully analyzed. The application of biotinylated rat liver cytosol proteins allowed discrimination between human

Discussion

In our experience, antibodies to SLA occur in roughly 40% of patients with AIH (Penner et al., unpublished data). Thus, it seemed of considerable interest to identify and characterize the relevant autoantigen(s).

SLA was originally defined as a non–species-, non–organ-specific antigen despite its highest concentration in liver and kidney.7 According to the published protocol it was obtained as a 150,000g supernatant,7 indicating its extremely high solubility and low molecular weight. Recently

References (29)

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Supported in part by Jubileumsfond grant 6668 from the Oesterreichische Nationalbank.

☆☆

Address requests for reprints to: Józefa Wȩsierska-Gądek, Ph.D., Institute of Tumor Biology–Cancer Research, University of Vienna, Borschkegasse 8 A, A-1090 Vienna, Austria. Fax: (43) 1-406-07-90; e-mail: Jozefa.Antonia.Gądek-Wę[email protected].

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