Pathogenesis of kidney disease in systemic lupus... : Current Opinion in Rheumatology (original) (raw)
Systemic lupus erythematosus and Sjögren's syndrome: Edited by Andras Perl
aDivision of Nephrology, Center for Immunity, Inflammation and Regenerative Medicine, USA
bMicrobiology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, USA
Correspondence to Dr Shu Man Fu, Department of Medicine, University of Virginia, School of Medicine, Box 800133, Charlottesville, VA 22908, USA Tel: +1 434 924 9627; fax: +1 434 924 9578; e-mail: [email protected]
Abstract
Purpose of review
A combination of systemic autoimmunity and tissue response to immune injury underlie renal involvement in lupus erythematosus. In this review, we discuss recent literature investigating pathogenetic mechanisms of lupus glomerulonephritis.
Recent findings
In lupus glomerulonephritis, glomerular immune complexes were believed to be the primary mediators of renal disease. Recent studies make it apparent that autoantibodies of multiple specificities participate in the formation of immune complexes, deposited in the kidneys. Renal infiltration by T cells, macrophages, and dendritic cells have a dominant role in the progression of lupus glomerulonephritis leading to renal failure. Activation of Toll-like receptors modulates autoantibody production and systemic interferon responses. However, glomerular cell responses to immune injury influence disease outcome. In addition, new insights on the genetics of susceptibility to end-organ damage in lupus glomerulonephritis have been discovered. Differential glomerular responses reflected in gene expression profiles during disease progression provide potential markers for diagnosis of lupus glomerulonephritis progression and flares. In addition, studies of end-organ responses provide new targets for therapeutic interventions.
Summary
Lupus glomerulonephritis is a prototype of immune complex disease mediated by autoantibodies of multiple specificities, one of which is anti-DNA. Murine models of spontaneous systemic lupus erythematosus have been critical for understanding the underlying disease. Recent studies demonstrate that in addition to systemic autoimmunity, end-organ responses, and end-organ resistance to damage are also critical in determining disease outcome. This understanding should influence design of novel therapeutic approaches in systemic lupus erythematosus.
© 2009 Lippincott Williams & Wilkins, Inc.