Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by a breakdown of immune tolerance and production of autoantibodies. Although the etiology of SLE remains to be fully elucidated, accumulating evidence suggests that genetic, environmental, infectious, and hormonal factors may predispose individuals to the development of SLE [1
]. This disease predominantly affects females of Afro-American, Hispanic, and Asian descent and can be mild or life threatening depending on the organs involved.
Renal involvement occurs in up to 60% of SLE patients and is a strong predictor of morbidity and mortality [4
]. Onset of lupus nephritis is initiated by the deposition of anti-double stranded (ds) DNA antibodies in the kidney parenchyma, which results in complement activation, infiltration of immune cells, and induction of inflammatory and fibrotic processes in the kidney. If these tissue-damaging processes are not sufficiently controlled, destruction of the normal kidney parenchyma and its replacement by fibrous tissue will ensue, which will lead to endstage renal failure [4
]. The exact mechanisms through which anti-dsDNA antibodies are deposited in the kidney to mediate kidney injury remains to be fully defined but current knowledge suggests that they can bind directly to mesangial cells through annexin II or α
] or indirectly to components of the glomerular basement membrane through nucleosomes [8
The extracellular matrix (ECM) was previously considered to function solely as a structural support that maintained the architecture of tissues and organs, but there is now compelling evidence to show that ECM components also play critical roles during inflammatory processes. Their accumulation and subsequent degradation is a cardinal feature of autoimmune diseases. Hyaluronan (HA) is a major component of the ECM that can directly regulate inflammatory processes through its interaction with CD44, its cell surface receptor [10
]. Depending on its molecular weight HA may possess either anti-inflammatory or pro-inflammatory properties. We have demonstrated that serum HA levels in patients with lupus nephritis correlate with disease activity, and that intrarenal HA expression is also increased in lupus nephritis, induced in part by anti-dsDNA antibodies [12
]. This paper will discuss the putative roles of HA and CD44 in SLE, with particular emphasis on their roles in mediating inflammatory processes during lupus nephritis.