International Immunology, Vol. 15, No. 9, pp. 1117-1124,
September 2003
© 2003 Japanese Society for Immunology
X-linked immunodeficient mice spontaneously produce lupus-related anti-RNA helicase A autoantibodies, but are resistant to pristane-induced lupus
1 Division of Rheumatology and Clinical Immunology, Department of Medicine, and 2 Department of Pathology, Immunology and Laboratory Medicine, University of Florida,Gainesville, FL 32610-0221, USA 3 Department of Medicine, Keio University School of Medicine, Tokyo 160-0016, Japan 4 First Department of Pathology, Fukushima Medical College, Fukushima 960-1247, Japan
Correspondence to: M. Satoh, Division of Rheumatology and Clinical Immunology, University of Florida, PO Box 100221, Gainesville, FL 32610-0221, USA. E-mail: satohm{at}medicine.ufl.edu
Transmitting editor: K. Yamamoto
Murine lupus can occur spontaneously or be induced by hydrocarbons, such as pristane. Spontaneous disease in MRL and NZB/W F1 mice is suppressed by the xid (X-linked immunodeficiency) mutation, which greatly diminishes T cell-independent type 2 responses as well as the number of peritoneal B1 cells. The present study asked whether lupus induced by i.p. injection of pristane likewise is inhibited by the xid defect. Male CBA/N (xid) mice were refractory to the induction of autoantibodies by pristane, whereas 23% of pristane-treated male CBA/CaJ controls produced anti-nRNP/Sm, -Su and/or -OJ (isoleucyl tRNA synthetase) antibodies. Unexpectedly, 43% (12 of 28) of the xid mice spontaneously produced anti-nuclear antibodies that proved highly specific for the lupus antigen RNA helicase A (RHA). Strikingly, this specificity was absent in CBA/CaJ mice (none of 51). Moreover, pristane treatment suppressed the production of anti-RHA antibodies when administered prior to the onset of autoantibody production, but enhanced anti-RHA levels when given after the onset of autoantibody production, suggesting that pristane interferes with anti-RHA production at an early stage. Large amounts of IgG1 anti-RHA autoantibodies were detected in the sera of xid mice, whereas pristane-induced anti-nRNP/Sm and -Su autoantibodies were almost exclusively IgG2a. Cytokine production within the peritoneal cavity reflected the predominant isotypes: IL-12 and IFN-
predominated in pristane-treated mice, whereas IL-4 and IL-6 were more predominant in untreated xid mice. The spontaneous production of anti-RHA by xid mice and its suppression by pristane treatment at the level of autoantibody induction supports the idea that lupus autoantibodies may be generated through a variety of mechanisms.
Keywords: autoantibodies, autoimmunity, cytokines, inflammation
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. O. Koppang, I. Bjerkas, E. Haugarvoll, E. K. L. Chan, N. J. Szabo, N. Ono, B. Akikusa, E. Jirillo, T. T. Poppe, H. Sveier, et al. Vaccination-Induced Systemic Autoimmunity in Farmed Atlantic Salmon J. Immunol., October 1, 2008; 181(7): 4807 - 4814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kuroda, J. Akaogi, D. C. Nacionales, S. C. Wasdo, N. J. Szabo, W. H. Reeves, and M. Satoh Distinctive Patterns of Autoimmune Response Induced by Different Types of Mineral Oil Toxicol. Sci., April 1, 2004; 78(2): 222 - 228. [Abstract] [Full Text] [PDF]
|
|