Liver, Pancreas, and Biliary TractMembers of the glutathione S-transferase gene family are antigens in autoimmune hepatitis☆,☆☆
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In our experience, antibodies to SLA occur in roughly 40% of patients with AIH (Penner et al., unpublished data).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
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2019, Free Radical Biology and MedicineSLA/LP/tRNP<sup>(Ser)Sec</sup> antigen in autoimmune hepatitis: Identification of the native protein in human hepatic cell extract
2010, Journal of AutoimmunityCitation Excerpt :Reactive sera were described to recognize either of the molecules [4] or both [7,8]. In 1998, Wesierska-Gadek et al. characterized SLA as a protein in the glutathione-S transferase complex, which has an important function in the detoxification of the liver [9]. Indeed, it could be shown that purified cytokeratins are not sufficient for the detection of anti-SLA [10].
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Supported in part by Jubileumsfond grant 6668 from the Oesterreichische Nationalbank.
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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].