PT  - JOURNAL ARTICLE
AU  - Kamala Vanarsa
AU  - Sanam Soomro
AU  - Ting Zhang
AU  - Briony Strachan
AU  - Claudia Pedroza
AU  - Malavika Nidhi
AU  - Pietro Cicalese
AU  - Christopher Gidley
AU  - Shobha Dasari
AU  - Shree Mohan
AU  - Nathan Thai
AU  - Van Thi Thanh Truong
AU  - Nicole Jordan
AU  - Ramesh Saxena
AU  - Chaim Putterman
AU  - Michelle Petri
AU  - Chandra Mohan
TI  - Quantitative planar array screen of 1000 proteins uncovers novel urinary protein biomarkers of lupus nephritis
AID  - 10.1136/annrheumdis-2019-216312
DP  - 2020 Oct 01
TA  - Annals of the Rheumatic Diseases
PG  - 1349--1361
VI  - 79
IP  - 10
4099  - http://ard.bmj.com/content/79/10/1349.short
4100  - http://ard.bmj.com/content/79/10/1349.full
SO  - Ann Rheum Dis2020 Oct 01; 79
AB  - Objective The goal of these studies is to discover novel urinary biomarkers of lupus nephritis (LN).Methods Urine from systemic lupus erythematosus (SLE) patients was interrogated for 1000 proteins using a novel, quantitative planar protein microarray. Hits were validated in an independent SLE cohort with inactive, active non-renal (ANR) and active renal (AR) patients, in a cohort with concurrent renal biopsies, and in a longitudinal cohort. Single-cell renal RNA sequencing data from LN kidneys were examined to deduce the cellular origin of each biomarker.Results Screening of 1000 proteins revealed 64 proteins to be significantly elevated in SLE urine, of which 17 were ELISA validated in independent cohorts. Urine Angptl4 (area under the curve (AUC)=0.96), L-selectin (AUC=0.86), TPP1 (AUC=0.84), transforming growth factor-β1 (TGFβ1) (AUC=0.78), thrombospondin-1 (AUC=0.73), FOLR2 (AUC=0.72), platelet-derived growth factor receptor-β (AUC=0.67) and PRX2 (AUC=0.65) distinguished AR from ANR SLE, outperforming anti-dsDNA, C3 and C4, in terms of specificity, sensitivity and positive predictive value. In multivariate regression analysis, urine Angptl4, L-selectin, TPP1 and TGFβ1 were highly associated with disease activity, even after correction for demographic variables. In SLE patients with serial follow-up, urine L-selectin (followed by urine Angptl4 and TGFβ1) were best at tracking concurrent or pending disease flares. Importantly, several proteins elevated in LN urine were also expressed within the kidneys in LN, either within resident renal cells or infiltrating immune cells, based on single-cell RNA sequencing analysis.Conclusion Unbiased planar array screening of 1000 proteins has led to the discovery of urine Angptl4, L-selectin and TGFβ1 as potential biomarker candidates for tracking disease activity in LN.