Comment on Vanarsa K, Soomro S, Zhang T, et al. Quantitative planar array screen of 1000 proteins uncovers novel urinary protein biomarkers of lupus nephritis. Ann Rheum Dis 2020; 79:1349-1361. Link: https://ard.bmj.com/content/79/10/1349
Commented by: Luís Sousa Inês, MD, PhD. CHUC Lupus Clinic, Rheumatology Department. Centro Hospitalar Universitário de Coimbra (CHUC). Coimbra, Portugal. Faculty of Health Sciences. University of Beira Interior. Covilhã, Portugal.
Discovering biomarkers of lupus nephritis (LN) from blood or urine could greatly facilitate longitudinal monitoring of SLE patients at regular intervals in order to closely track and predict LN disease activity, progression and treatment response to guide tailored therapy accordingly. So far, many studies have failed to find biomarkers of LN reliable for use in clinical practice. In this study by Vanarsa et al., it was used a novel microarray to screen and quantify 1000 proteins in the urine of 24 subjects (15 with active SLE and 9 healthy controls) in order to identify potential urinary biomarkers for renal involvement in patients with SLE. Screening revealed 64 proteins to be significantly elevated in SLE urine, of which 17 were selected for ELISA validation in an independent cohort of 78 subjects (SLE patients with inactive, active non-renal and active LN, and healthy controls), a cohort of 20 LN patients with concurrent renal biopsies, a longitudinal cohort of 7 SLE patients, and a cohort of 47 non-SLE patients with chronic kidney disease. Emerged as novel biomarkers in the urine: Angptl4, L-selectin, TPP1, TGFβ1, TSP-1, FOLR2 and PDGF-Rβ, that successfully distinguished active LN patients from active non-renal lupus patients. Urine Angptl4, L-selectin and TPP1, in combination, offered the best discrimination of active LN from active non-renal SLE, with an area under the receiver operating curves of 0.97.
This study uncovers novel urinary protein biomarkers that shows promise at tracking concurrent or pending LN flares. Additional longitudinal studies with larger sample size and more representative of the SLE population is warranted to investigate how these urinary molecules relate to renal pathology, disease progression, treatment response over time and long-term renal and patient outcome.
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