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

Samantha Stanley; Kamala Vanarsa; Samar Soliman; Deena Habazi; Claudia Pedroza; Gabriel Gidley; Ting Zhang; Shree Mohan; Evan Der; Hemant Suryawanshi; Thomas Tuschl; Jill Buyon; Chaim Putterman; Chi Chiu Mok; Michelle Petri; Ramesh Saxena; Chandra Mohan

doi:10.1038/s41467-020-15986-3

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

Samantha Stanley, Kamala Vanarsa, Samar Soliman, Deena Habazi, Claudia Pedroza, Gabriel Gidley, Ting Zhang, Shree Mohan, Evan Der, Hemant Suryawanshi, Thomas Tuschl, Jill Buyon, Chaim Putterman, Chi Chiu Mok, Michelle Petri, Ramesh Saxena, Chandra Mohan

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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.

Original language	English
Article number	2197
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15986-3
State	Published - 4 May 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Funding

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.

Funders	Funder number
National Institutes of Health	P30DK079328, AR069572
National Institute of Arthritis and Musculoskeletal and Skin Diseases	R01AR074096

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Stanley, S., Vanarsa, K., Soliman, S., Habazi, D., Pedroza, C., Gidley, G., Zhang, T., Mohan, S., Der, E., Suryawanshi, H., Tuschl, T., Buyon, J., Putterman, C., Mok, C. C., Petri, M., Saxena, R., & Mohan, C. (2020). Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities. Nature Communications, 11(1), Article 2197. https://doi.org/10.1038/s41467-020-15986-3

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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.",

author = "Samantha Stanley and Kamala Vanarsa and Samar Soliman and Deena Habazi and Claudia Pedroza and Gabriel Gidley and Ting Zhang and Shree Mohan and Evan Der and Hemant Suryawanshi and Thomas Tuschl and Jill Buyon and Chaim Putterman and Mok, {Chi Chiu} and Michelle Petri and Ramesh Saxena and Chandra Mohan",

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Stanley, S, Vanarsa, K, Soliman, S, Habazi, D, Pedroza, C, Gidley, G, Zhang, T, Mohan, S, Der, E, Suryawanshi, H, Tuschl, T, Buyon, J, Putterman, C, Mok, CC, Petri, M, Saxena, R & Mohan, C 2020, 'Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities', Nature Communications, vol. 11, no. 1, 2197. https://doi.org/10.1038/s41467-020-15986-3

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AU - Vanarsa, Kamala

AU - Soliman, Samar

AU - Habazi, Deena

AU - Pedroza, Claudia

AU - Gidley, Gabriel

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AU - Mohan, Shree

AU - Der, Evan

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AU - Tuschl, Thomas

AU - Buyon, Jill

AU - Putterman, Chaim

AU - Mok, Chi Chiu

AU - Petri, Michelle

AU - Saxena, Ramesh

AU - Mohan, Chandra

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

Abstract

Bibliographical note

Funding

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