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Dialogue: A blissful future for lupus nephritis: harnessing repeat kidney biopsies to identify meaningful biomarkers of disease
  1. Fernanda Payan Schober1 and
  2. William F Pendergraft III1,2
  1. 1Division of Nephrology, Department of Medicine, University of North Carolina (UNC) Kidney Center, Chapel Hill, North Carolina, USA
  2. 2The Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
  1. Correspondence to Dr Will Pendergraft; will_pendergraft{at}med.unc.edu

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Kidney involvement in patients with systemic lupus erythematosus (SLE) portends a worse prognosis; thus, early and accurate detection of lupus nephritis is key. Unfortunately, current clinical markers, including creatinine clearance, autoantibodies, serum complement levels, urine sediment and proteinuria, do not always reliably identify patients with kidney disease. Moreover, these biomarkers do not help distinguish between various histopathological classes of lupus nephritis, which are often used as benchmarks to guide treatment. An intensely hot area of lupus research currently revolves around biased and unbiased approaches to identify biomarkers that can more reliably predict clinical and histopathological lupus-associated kidney activity and, perhaps even more importantly, durable response to treatment.

Novel biomarkers of lupus nephritis currently under investigation include but are not limited to B Lymphocyte Stimulator (BLyS), A Proliferation-Inducing Ligand (APRIL), tumor necrosis factor (TNF)-like WEAK inducer of apoptosis (TWEAK), and Monocyte Chemoattractant Protein-1 (MCP-1). BLyS, also known as B cell Activating Factor belonging to the TNF Family (or BAFF), is a transmembrane protein that is cleaved by a furin protease into a biologically active soluble protein that is important for B cell activation and differentiation. Numerous studies have shown that serum BLyS levels are elevated in patients with SLE compared with controls, making it the target of the recently Food and Drug Administration (FDA)-approved lupus drug, belimumab.1 Currently, the Belimumab International Lupus Nephritis Study clinical trial is underway to determine the efficacy of belimumab in patients with lupus nephritis (http://www.clinicaltrials.gov, NCT01639339). Like BLyS, APRIL is a member of the TNF family, and is thought to have a regulatory role in B cell proliferation. APRIL levels have been shown to be elevated in patients with lupus compared with healthy controls, although one study has found that levels may be lower in patients with lupus nephritis compared with patients who have …

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