RT Journal Article
SR Electronic
T1 Quantitative planar array screen of 1000 proteins uncovers novel urinary protein biomarkers of lupus nephritis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1349
OP 1361
DO 10.1136/annrheumdis-2019-216312
VO 79
IS 10
A1 Kamala Vanarsa
A1 Sanam Soomro
A1 Ting Zhang
A1 Briony Strachan
A1 Claudia Pedroza
A1 Malavika Nidhi
A1 Pietro Cicalese
A1 Christopher Gidley
A1 Shobha Dasari
A1 Shree Mohan
A1 Nathan Thai
A1 Van Thi Thanh Truong
A1 Nicole Jordan
A1 Ramesh Saxena
A1 Chaim Putterman
A1 Michelle Petri
A1 Chandra Mohan
YR 2020
UL http://ard.bmj.com/content/79/10/1349.abstract
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.