HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Migliaccio, C. Articles by Gershwin, M. E. Search for Related Content PubMed PubMed Citation Articles by Migliaccio, C. Articles by Gershwin, M. E. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Bile Duct Diseases Cirrhosis

Monoclonal Antibodies to Mitochondrial E2 Components Define Autoepitopes in Primary Biliary Cirrhosis¹

Christopher Migliaccio^*, Akiyoshi Nishio^*, Judy Van de Water^*, Aftab A. Ansari, Patrick S. C. Leung^*, Yasuni Nakanuma, Ross L. Coppel^§ and M. Eric Gershwin^2,*

^* Division of Rheumatology, Allergy and Clinical Immunology, University of California School of Medicine, Davis, CA 95616; Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322; Department of Pathology, Kanazawa University, School of Medicine, Kanazawa, Japan; and ^§ Department of Microbiology, Monash University, Clayton, Victoria, Australia

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of antimitochondrial Abs (AMA). The autoantigens recognized by AMA are the E2 components of the pyruvate dehydrogenase complex (PDC-E2), the branched chain 2-oxoacid dehydrogenase complex E (BCOADC-E2), and the 2-oxoglutarate dehydrogenase complex E (OGDC-E2). Previous studies using murine monoclonal and human combinatorial Abs to PDC-E2 have demonstrated an intense linear staining pattern in the apical region of biliary epithelial cells (BEC) in PBC but not control liver. We therefore examined whether mAbs to the other mitochondrial autoantigens BCOADC-E2 and OGDC-E2 demonstrated disease-specific patterns of reactivity. Using an expressed recombinant "trihybrid" protein containing the lipoyl domains of PDC-E2, OGDC-E2, and BCOADC-E2, we immunized BALB/c mice to produce 35 mAbs specific for one or more of the above mitochondrial autoantigens. Seven of these mAbs uniquely stained the apical region of BEC in PBC. Of these seven, one was reactive to PDC-E2, two recognized BCOADC-E2, three were reactive to OGDC-E2, and one recognized all three Ags. Our current data demonstrate that, similar to our previous studies regarding PDC-E2, mAbs to BCOADC-E2 and OGDC-E2, or a molecule that cross-reacts with the inner lipoyl domain of all three enzymes, also show a uniquely intense staining pattern in the apical region of BEC in patients with PBC when compared with diseased controls. The abundance of such disease-specific determinants in the target cells of PBC raises interesting possibilities regarding the role of these autoantigens in the pathogenesis of this disease.

This article has been cited by other articles:

				J. Mazumdar, E. H. Wilson, K. Masek, C. A. Hunter, and B. Striepen Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii PNAS, August 29, 2006; 103(35): 13192 - 13197. [Abstract] [Full Text] [PDF]

				J. Irie, Y. Wu, L. S. Wicker, D. Rainbow, M. A. Nalesnik, R. Hirsch, L. B. Peterson, P. S.C. Leung, C. Cheng, I. R. Mackay, et al. NOD.c3c4 congenic mice develop autoimmune biliary disease that serologically and pathogenetically models human primary biliary cirrhosis J. Exp. Med., May 15, 2006; 203(5): 1209 - 1219. [Abstract] [Full Text] [PDF]

				K. Amano, P. S. C. Leung, R. Rieger, C. Quan, X. Wang, J. Marik, Y. F. Suen, M. J. Kurth, M. H. Nantz, A. A. Ansari, et al. Chemical Xenobiotics and Mitochondrial Autoantigens in Primary Biliary Cirrhosis: Identification of Antibodies against a Common Environmental, Cosmetic, and Food Additive, 2-Octynoic Acid J. Immunol., May 1, 2005; 174(9): 5874 - 5883. [Abstract] [Full Text] [PDF]

				H. Habelhah, A. Laine, H. Erdjument-Bromage, P. Tempst, M. E. Gershwin, D. D. L. Bowtell, and Z. Ronai Regulation of 2-Oxoglutarate ({alpha}-Ketoglutarate) Dehydrogenase Stability by the RING Finger Ubiquitin Ligase Siah J. Biol. Chem., December 17, 2004; 279(51): 53782 - 53788. [Abstract] [Full Text] [PDF]

				K. Amano, P. S. C. Leung, Q. Xu, J. Marik, C. Quan, M. J. Kurth, M. H. Nantz, A. A. Ansari, K. S. Lam, M. Zeniya, et al. Xenobiotic-Induced Loss of Tolerance in Rabbits to the Mitochondrial Autoantigen of Primary Biliary Cirrhosis Is Reversible J. Immunol., May 15, 2004; 172(10): 6444 - 6452. [Abstract] [Full Text] [PDF]

				S. A. Long, C. Quan, J. Van de Water, M. H. Nantz, M. J. Kurth, D. Barsky, M. E. Colvin, K. S. Lam, R. L. Coppel, A. Ansari, et al. Immunoreactivity of Organic Mimeotopes of the E2 Component of Pyruvate Dehydrogenase: Connecting Xenobiotics with Primary Biliary Cirrhosis J. Immunol., September 1, 2001; 167(5): 2956 - 2963. [Abstract] [Full Text] [PDF]