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Liver membrane autoantibodies in chronic active hepatitis. Studies on mechanically and enzymatically isolated rabbit
G Gerken1, M Manns, G Ramadori
1Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität, Mainz, F.R.G.
Abstract:
Target antigens relevant for immune reactions in inflammatory liver diseases should be expressed on the hepatocellular membrane. Using mechanically or enzymatically isolated rabbit hepatocytes, we evaluated the influence of cell integrity on the detection of membrane-expressed antigens by sera from patients with chronic hepatitis and by murine monoclonal antibodies. Our results provide evidence that target antigens of liver membrane autoantibodies (LMA) as well as liver kidney microsomal antibodies (LKM) are not expressed on the hepatocellular membrane of viable and intact isolated rabbit hepatocytes. However, LMA were detected in the sera of 56% of patients with autoimmune chronic active hepatitis using mechanically isolated hepatocytes. These findings underline the diagnostic relevance of the autoantibodies. It is suggested that LMA are directed against constituents of the cytoskeleton. Therefore, it seems to be unlikely that this antibody is causally involved in the pathogenesis of autoimmune liver diseases.
Insights
Autoimmune liver disease antibodies, liver membrane autoantibodies (LMA) and liver kidney microsomal antibodies (LKM), are not found on intact liver cells. However, LMA detection in patients suggests diagnostic relevance, possibly targeting cytoskeleton components.
Area of Science:
- Hepatology and Immunology
- Autoimmune Liver Diseases Research
- Cellular Immunology and Antigen Expression
Background:
- Immune reactions in inflammatory liver diseases often target antigens on the hepatocellular membrane.
- Accurate detection of these membrane-expressed antigens is crucial for diagnosing autoimmune liver conditions.
- The integrity of isolated hepatocytes can influence antigen accessibility and antibody binding.
Purpose of the Study:
- To investigate the expression of target antigens for liver membrane autoantibodies (LMA) and liver kidney microsomal antibodies (LKM) on isolated rabbit hepatocytes.
- To evaluate the impact of hepatocyte integrity (mechanical vs. enzymatic isolation) on the detection of these autoantibodies.
- To clarify the diagnostic relevance and potential pathogenetic role of LMA in autoimmune liver diseases.
Main Methods:
- Isolation of rabbit hepatocytes using mechanical and enzymatic methods to assess cell integrity.
- Detection of autoantibodies (LMA and LKM) in sera from patients with chronic hepatitis using immunofluorescence assays.
- Utilized murine monoclonal antibodies to further characterize antigen expression on hepatocytes.
Main Results:
- Target antigens for both LMA and LKM were not found on the hepatocellular membrane of viable, intact isolated rabbit hepatocytes.
- LMA were detected in 56% of patients with autoimmune chronic active hepatitis when using mechanically isolated hepatocytes.
- These findings suggest LMA may target intracellular cytoskeleton components rather than membrane-expressed antigens.
Conclusions:
- The study challenges the notion that LMA and LKM target membrane-expressed antigens on intact hepatocytes.
- The diagnostic utility of LMA in autoimmune chronic active hepatitis is supported, particularly with mechanically isolated cells.
- LMA are likely directed against cytoskeleton constituents, suggesting a non-pathogenic role in autoimmune liver disease.