New markers off diisease acttiiviitty iin llupus nephriittiis::

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by production of autoantibodies against a broad range of selfantigens including DNA, RNA, histones and other nuclear components.In most patients, vital organs and tissues are often implicated, including kidney, brain, cardiovascular, joint and skin.Lupus nephritis (LN) is a common and serious complication in SLE and is associated with significant mortality and morbidity of SLE patients.Generally, 74% of lupus patients will develop clinically relevant nephritis at some time in the course of their illness.The pathogenesis of LN is a complex process, involving deposition of autoantibodies in the glomerulus, activation of complement and macrophages, cell proliferation, production of extracellular matrix proteins, pro-inflammatory cytokines and chemokines, which are then linked through multiple mechanisms to cause tubular damage, tubulointerstitial inflammation and fibrosis.Autoantibodies and ICs are important first mediators that are required for disease expression in human disease. Deposition of ICs, however, is not sufficient for disease expression, as numerous studies report lack of proliferative disease despite significant IgG/IC deposition in glomeruli.Downstream mediators are blocked in these pharmacologic/genetic studies, inhibiting disease activity without impacting IC deposition.Complement, TLRs and FcγRs play an amplification role in the initiation and propagation of disease.IC deposition with complement, TLR and/or FcγR activation stimulates intrinsic immune active glomerular cells to release inflammatory cytokines and chemoattractant chemokines, resulting in the influx of the spectrum of infl ammatory cells.The end mediators of disease appear to be the reactive intermediates produced by both inflammatory cells and intrinsic glomerular cells.Although tissue repair post inflammatory injury is also probably a key prognostic process, very little is known regarding factors involved in tissue repair. These multiple mediators provide a host of targets for therapeutic intervention. Only 50% of patients respond to current standards of therapy.Clearly there is room for improvement, but no one therapy will probably be effective in most patients. Determining which pathway is key to a given patient is the challenge for the immediate future, as well as developing safe mechanisms for blocking these pathways.So far, LN remains a major challenge and continues to be one of the most severe manifestations of SLE.The medical therapy for LN depends on the - 82 - severity of the disease.Thus, finding reliable biomarkers for LN will help to evaluate disease activity, identify patients at risk for kidney damage and facilitate early diagnosis and intervention to improve favorable outcomes.Multiple lines of evidence have supported a genetic etiology in SLE and LN.Linkage analysis and Genome-wide association studies (GWAS) have been used for screening lupus susceptibility and analyses of common genetic variants in lupus have revealed a number of susceptibility loci.Nonetheless, the cumulative effect of these loci accounts for only a fraction of disease heritability.Other heritable factors of complex human disease may broadly reside in epigenetic mechanisms. Epigenetics