Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities

S Stanley, K Vanarsa, S Soliman, D Habazi… - Nature …, 2020 - nature.com
S Stanley, K Vanarsa, S Soliman, D Habazi, C Pedroza, G Gidley, T Zhang, S Mohan, E Der…
Nature communications, 2020nature.com
Emerging urinary biomarkers continue to show promise in evaluating lupus nephritis (LN).
Here, we screen urine from active LN patients for 1129 proteins using an aptamer-based
platform, followed by ELISA validation in two independent cohorts comprised of 127 inactive
lupus, 107 active LN, 67 active non-renal lupus patients and 74 healthy controls, of three
different ethnicities. Urine proteins that best distinguish active LN from inactive disease are
ALCAM, PF-4, properdin, and VCAM-1 among African-Americans, sE-selectin, VCAM-1, BFL …
Abstract
Emerging urinary biomarkers continue to show promise in evaluating lupus nephritis (LN). Here, we screen urine from active LN patients for 1129 proteins using an aptamer-based platform, followed by ELISA validation in two independent cohorts comprised of 127 inactive lupus, 107 active LN, 67 active non-renal lupus patients and 74 healthy controls, of three different ethnicities. Urine proteins that best distinguish active LN from inactive disease are ALCAM, PF-4, properdin, and VCAM-1 among African-Americans, sE-selectin, VCAM-1, BFL-1 and Hemopexin among Caucasians, and ALCAM, VCAM-1, TFPI and PF-4 among Asians. Most of these correlate significantly with disease activity indices in the respective ethnic groups, and surpass conventional metrics in identifying active LN, with better sensitivity, and negative/positive predictive values. Several elevated urinary molecules are also expressed within the kidneys in LN, based on single-cell RNAseq analysis. Longitudinal studies are warranted to assess the utility of these biomarkers in tracking lupus nephritis.
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