TY - JOUR
T1 - Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities
AU - Stanley, Samantha
AU - Vanarsa, Kamala
AU - Soliman, Samar
AU - Habazi, Deena
AU - Pedroza, Claudia
AU - Gidley, Gabriel
AU - Zhang, Ting
AU - Mohan, Shree
AU - Der, Evan
AU - Suryawanshi, Hemant
AU - Tuschl, Thomas
AU - Buyon, Jill
AU - Putterman, Chaim
AU - Mok, Chi Chiu
AU - Petri, Michelle
AU - Saxena, Ramesh
AU - Mohan, Chandra
N1 - Funding Information:
We acknowledge the support of NIH RO1 AR074096 and AR069572. The Hopkins Lupus Cohort is supported by NIH Grant RO1 AR069572. The UT Southwestern cohort is supported by the George M. O’Brien Kidney Research Core Center NIH P30DK079328.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41467-020-15986-3
DO - 10.1038/s41467-020-15986-3
M3 - Article
C2 - 32366845
AN - SCOPUS:85084235042
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2197
ER -