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

Nat Commun. 2020 May 4;11(1):2197. doi: 10.1038/s41467-020-15986-3.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / urine
  • Adult
  • Aptamers, Peptide / metabolism*
  • Asian People / statistics & numerical data
  • Biomarkers / urine*
  • Black or African American / statistics & numerical data
  • E-Selectin / analysis
  • Female
  • Humans
  • Lupus Nephritis / diagnosis*
  • Lupus Nephritis / ethnology
  • Lupus Nephritis / urine
  • Properdin / urine
  • Proteins / analysis*
  • Sensitivity and Specificity
  • Vascular Cell Adhesion Molecule-1 / urine
  • White People / statistics & numerical data
  • Young Adult

Substances

  • Activated-Leukocyte Cell Adhesion Molecule
  • Aptamers, Peptide
  • Biomarkers
  • E-Selectin
  • Proteins
  • Vascular Cell Adhesion Molecule-1
  • Properdin