The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Leung, P. S. C.
Right arrow Articles by Gershwin, M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leung, P. S. C.
Right arrow Articles by Gershwin, M. E.
The Journal of Immunology, 2003, 170: 5326-5332.
Copyright © 2003 by The American Association of Immunologists

Immunization with a Xenobiotic 6-Bromohexanoate Bovine Serum Albumin Conjugate Induces Antimitochondrial Antibodies1

Patrick S. C. Leung*, Chao Quan{dagger}, Ogyi Park*, Judy Van de Water*, Mark J. Kurth{dagger}, Michael H. Nantz{dagger}, Aftab A. Ansari{ddagger}, Ross L. Coppel§, Kit S. Lam and M. Eric Gershwin2,*

* Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, and {dagger} Department of Chemistry, University of California, Davis, CA 95616; {ddagger} Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322; § Department of Microbiology, Monash University, Clayton, Victoria, Australia; and Division of Hematology/Oncology, University of California, Sacramento Medical Center, Sacramento, CA 95817

The E2 subunit of pyruvate dehydrogenase complex (PDC-E2) is the major autoantigen recognized by antimitochondrial Abs (AMA) in primary biliary cirrhosis (PBC). Recently, we replaced the lipoic acid moiety of PDC-E2 with a battery of synthetic structures designed to mimic a xenobiotically modified lipoyl hapten on a 12-aa peptide that was found within the immunodominant autoepitope of PDC-E2 and demonstrated that AMA in PBC reacted against several organic modified mimotopes as well as, or sometimes significantly better than, the native lipoyl domain. Based on this data, we immunized rabbits with one such xenobiotic organic compound, 6-bromohexanoate, coupled to BSA. One hundred percent of immunized rabbits developed AMA that have each and every characteristic of human AMAs with reactivity against PDC-E2, E2 subunit of branched chain 2-oxo-acid dehydrogenase, and E2 subunit of 2-oxoglutarate dehydrogenase complex. The rabbit AMA also inhibited enzymatic function of PDC-E2 and, importantly, binds to peptide sequences not present in the xenobiotic carrier immunogen. In contrast, BSA-immunized controls did not produce such activity. Our observation that animals immunized with a xenobiotic BSA complex produce autoantibodies that react not only with the xenobiotic, but also with mitochondrial autoantigens recognized by autoimmune PBC sera, suggests that environmental xenobiotic agents can be a risk factor for the induction of PBC.




This article has been cited by other articles:


Home page
 Postgrad. Med. J.Home page
D E J Jones
Pathogenesis of primary biliary cirrhosis
Postgrad. Med. J., January 1, 2008; 84(987): 23 - 33.
[Full Text] [PDF]

Home page
 GutHome page
D. E J Jones
Pathogenesis of Primary Biliary Cirrhosis
Gut, November 1, 2007; 56(11): 1615 - 1624.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
P. S. C. Leung, O. Park, K. Tsuneyama, M. J. Kurth, K. S. Lam, A. A. Ansari, R. L. Coppel, and M. E. Gershwin
Induction of Primary Biliary Cirrhosis in Guinea Pigs following Chemical Xenobiotic Immunization
J. Immunol., August 15, 2007; 179(4): 2651 - 2657.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. Bellucci, S. Oertelt, M. Gallagher, S. Li, E. Zorn, E. Weller, F. Porcheray, E. P. Alyea, R. J. Soiffer, N. C. Munshi, et al.
Differential epitope mapping of antibodies to PDC-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis
Blood, March 1, 2007; 109(5): 2001 - 2007.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
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]

Home page
 NEJMHome page
M. M. Kaplan and M. E. Gershwin
Primary Biliary Cirrhosis
N. Engl. J. Med., September 22, 2005; 353(12): 1261 - 1273.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.