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Chapter 101 : Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis

Authors: Patrick S. C. Leung1, Michael P. Manns2, Ross L. Coppel3, M. Eric Gershwin4
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Affiliations: 1: Division of Rheumatology/Allergy and Clinical Immunology, Genome and Biomedical Sciences Facility Suite 6510, School of Medicine, University of California at Davis, Davis, CA 95616; 2: Department of Gastroenterology and Hepatology, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Hannover, Germany; 3: Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia 3800; 4: Division of Rheumatology/Allergy and Clinical Immunology, Genome and Biomedical Sciences Facility Suite 6510, School of Medicine, University of California at Davis, Davis, CA 95616
Content Type: Reference
Publication Year: 2016

Category: Immunology

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Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, Page 1 of 2

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Abstract:

The immunodetection of autoantibodies in autoimmune liver disease has been technically difficult because of the following: (i) serum autoantibodies from these patients usually react to a broad spectrum of antigens; (ii) some of these autoantibodies may have low titers; (iii) the biochemical nature of these autoantigens is unknown; and (iv) many autoantigens have low concentrations, and their biochemical purification often requires sophisticated procedures. The development and application of immunohistochemical, biochemical, and molecular biological techniques have provided new approaches to the study of autoimmune diseases and, in particular, the immunological detection of autoantigens. This is exemplified by two autoimmune diseases of the liver, namely, primary biliary cholangitis (PBC, formerly known as primary biliary cirrhosis) and autoimmune hepatitis (AIH). This chapter focuses on the detection of antimitochondrial autoantibodies (AMA) in PBC and the detection of liver kidney microsomal (LKM) antibodies in AIH.

Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101
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Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis
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Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101
/content/10.1128/9781555818722.ch101.ch101fig1
FIGURE 1

Detection of AMA by IF on HEp-2 cells. Note the characteristic mitochondrial staining pattern by PBC sera.

10.1128/9781555818722/8722ch101fig1_thmb.gif
10.1128/9781555818722/8722ch101fig1.gif
Image of FIGURE 1
FIGURE 1

Detection of AMA by IF on HEp-2 cells. Note the characteristic mitochondrial staining pattern by PBC sera.

Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101
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FIGURE 2

Reactivities of PBC sera with bovine heart mitochondria. Bovine heart mitochondria were resolved by SDS-PAGE, transferred to a nitrocellulose filter, and tested for reactivity with PBC sera (lanes A to F). Note the different patterns of AMA reactivities from various patients with PBC to the 70-kDa pyruvate dehydrogenase E2 subunit, the 52-kDa branched-chain 2-oxo-acid dehydrogenase E2 subunit, the 48-kDa 2-oxo-acid dehydrogenase E2 subunit, and the 41-kDa pyruvate dehydrogenase E1alpha subunit.

10.1128/9781555818722/8722ch101fig2_thmb.gif
10.1128/9781555818722/8722ch101fig2.gif
Image of FIGURE 2
FIGURE 2

Reactivities of PBC sera with bovine heart mitochondria. Bovine heart mitochondria were resolved by SDS-PAGE, transferred to a nitrocellulose filter, and tested for reactivity with PBC sera (lanes A to F). Note the different patterns of AMA reactivities from various patients with PBC to the 70-kDa pyruvate dehydrogenase E2 subunit, the 52-kDa branched-chain 2-oxo-acid dehydrogenase E2 subunit, the 48-kDa 2-oxo-acid dehydrogenase E2 subunit, and the 41-kDa pyruvate dehydrogenase E1alpha subunit.

Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101
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FIGURE 3

Detection of LKM antibodies and AMA by IF on cryostat rat liver and kidney sections. (A) Staining of liver lobule by LKM-1 antibodies. (B) Staining of proximal renal tubules by LKM-1 antibodies.

10.1128/9781555818722/8722ch101fig3_thmb.gif
10.1128/9781555818722/8722ch101fig3.gif
Image of FIGURE 3
FIGURE 3

Detection of LKM antibodies and AMA by IF on cryostat rat liver and kidney sections. (A) Staining of liver lobule by LKM-1 antibodies. (B) Staining of proximal renal tubules by LKM-1 antibodies.

Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101
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Tables

Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis
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Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101
/content/10.1128/9781555818722.ch101.ch101tab1
TABLE 1

Summary of 2-oxo-acid dehydrogenase mitochondrial antigens in PBC

Generic image for table
TABLE 1

Summary of 2-oxo-acid dehydrogenase mitochondrial antigens in PBC

Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101
/content/10.1128/9781555818722.ch101.ch101tab2
TABLE 2

Clinical characteristics of primary biliary cholangitis

Generic image for table
TABLE 2

Clinical characteristics of primary biliary cholangitis

Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101
/content/10.1128/9781555818722.ch101.ch101tab3
TABLE 3

Diagnostic criteria for AIH

Generic image for table
TABLE 3

Diagnostic criteria for AIH

Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101
/content/10.1128/9781555818722.ch101.ch101tab4
TABLE 4

Heterogeneity of microsomal antigens

Generic image for table
TABLE 4

Heterogeneity of microsomal antigens

Citation: Leung P, Manns M, Coppel R, Gershwin M. 2016. Detection of Antimitochondrial Autoantibodies in Primary Biliary Cholangitis and Liver Kidney Microsomal Antibodies in Autoimmune Hepatitis, p 966-974. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch101

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