New insights from murine lupus: disassociation of autoimmunity and end organ damage and the role of T cells.
OBJECTIVE
This review summarizes current literature on genetic regulation of different phenotypes in systemic lupus erythematosus in context of end-organ disease. Recent findings conflicting with the current paradigm that loss of tolerance to chromatin is the critical step for end-organ injury are discussed.


RESULTS
Systemic lupus erythematosus is a prototype immune complex disease with circulating autoantibodies to chromatin, histone proteins, Sm/La, and other nuclear and cytoplasmic proteins. Extensive studies have been carried out on the regulation of B-cell and autoantibody production in lupus mice. However, the hypothesis that autoantibodies are primary mediators of organ damage fails to explain the heterogenous presentation in patients. Studies in murine models of systemic lupus erythematosus clearly dissociate genetic control of autoantibody responses to classic lupus antigens and kidney disease. There is increasing evidence to support the role of autoreactive T cells and genetic control of end organ susceptibility. These studies suggest complex interactions between innate and adaptive immunity resulting in end-organ damage. This review focuses on autoimmune responses and renal involvement in spontaneous systemic lupus erythematosus using murine models of lupus nephritis.


CONCLUSIONS
Studies in murine models demonstrate complex genetic interactions regulating spontaneous systemic lupus erythematosus. Although detection of serum autoantibodies is considered a hallmark for clinical diagnosis of systemic lupus erythematosus, recent evidence shows that autoantibodies to classic lupus antigens are neither required nor sufficient for end-organ damage. Thus, murine models provide new insights into the pathogenesis of systemic lupus erythematosus.
Bagavant
Harini
H
Specialized Center of Research on Systemic Lupus Erythematosus, University of Virginia, Charlottesville, 22908, USA.
Fu
Shu Man
SM
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*