| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Section of Nephrology, Department of Medicine, The University of Illinois, Chicago, IL 60612;
Division of Rheumatology, Department of Medicine, The Research Institute of the McGill University Health Centre,
Department of Pathology, Jewish General Hospital, and
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada;
¶ Department of Pathology, Peel Memorial Hospital, William Osler Health Centre, Brampton, Ontario, and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, and
|| Department of Medicine and Department of Immunology, Toronto Western Hospital Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada
The initial events predisposing to loss of tolerance in patients with systemic lupus erythematosus (SLE) are largely unknown, as are the events that precipitate the transition from preclinical to overt disease. We hypothesized that induction of murine SLE would require tipping the balance between tolerance and immunity in two ways: 1) an immunogen that could take advantage of apoptotic cells as a scaffold for epitope spread, and 2) an immune activator that would generate a strong and persistent T cell response to the inciting immunogen. We show that immunization of C57BL/6 and BALB/c mice with human 
2-glycoprotein I, an apoptotic cell-binding protein, in the presence of LPS induces a long-lived, potent response to 2-glycoprotein I that results in epitope spread to multiple SLE autoantigens. SLE-specific autoantibodies emerged in a sequential manner that recapitulated the order seen in human SLE. Moreover, immunized mice developed overt glomerulonephritis closely resembling human lupus nephritis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grants DK59793 and HL69722 from the National Institutes of Health (to J.S.L.), a Young Investigator Award from the National Kidney Foundation of Illinois (to J.S.L.), Grant TAS97/0009 from the Arthritis Society of Canada (to J.R.), and Grant MOP-67101 from the Canadian Institutes for Health Research (to J.R.).
2 J.S.L. and R.S. contributed equally to this research.
3 Current address: Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10040.
4 Address correspondence and reprint requests to Dr. Joyce Rauch, The Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada. E-mail address: joyce.rauch{at}mcgill.ca
5 Abbreviations used in this paper: SLE, systemic lupus erythematosus; CL, cardiolipin; aCL, anticardiolipin; 2GPI, 2-glycoprotein I; ANA, antinuclear Ab; nRNP, nuclear ribonucleoprotein; PC, phosphatidylcholine; PEth, phosphatidylethanolamine; PS, phosphatidylserine; Sm, Smith Ag; aPL, antiphospholipid; aPTT, activated partial thromboplastin time; NMS, normal mouse serum.
This article has been cited by other articles:
|
|
 |
|
  S Muller, J Dieker, A Tincani, and P. Meroni Pathogenic anti-nucleosome antibodies Lupus, May 1, 2008; 17(5): 431 - 436. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
