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Abstract
Background There is an urgent need to identify novel biomarkers for lupus nephritis (LN) in disease diagnosis, assessment, monitoring, and prognosis prediction. Here, we report a new non-invasive urinary biomarker, L-selectin, in two independent multiple-ethnicity SLE cohorts from three centers.
Methods Urinary L-selectin (uL-selectin) was tested cross-sectionally in a Chinese-based cohort (n=255) and a US-based cohort (n=223) of SLE patients and controls using ELISA. A longitudinal cohort includes eighteen active Chinese LN patients who were followed up for a minimum of 6 months.
Results In the Chinese cross-sectional cohort, uL-selectin was significantly increased in active lupus nephritis (aLN) patients compared with active non-renal SLE patients (aNR), inactive LN patients (iLN), inactive non-renal SLE patients, chronic kidney disease (CKD) patients, and healthy controls (HC) (all p < 0.0001) (table 1, figure 1A). uL-selectin positively correlated with global and renal disease activities (all p < 0.0001) and was significantly associated with activity index (AI) and chronicity index (CI) (figure 1E-F). It also correlated with conventional metrics (serum C3, anti-dsDNA and 24h proteinuria) and histological characteristics (figure 1G). Univariate and multivariate logistic regression analyses revealed low uL-selectin as an independent risk factor for high CI (CI>3) (figure 1J). Similar results were noted in the US-based cohort consisting of Caucasian, African American and Hispanic subjects (figure 1B-D). In a longitudinal cohort of LN patients, uL-selectin levels decreased at the end of follow up in the remission group (p=0.001), but not in non-remission patients (p=0.58) (figure 1H-I).
Conclusions uL-selectin is a novel biomarker of clinical disease activity and renal histopathology in LN across multiple ethnicities. It also reflects treatment response in LN patients during follow up.
Comparison of uL-selectin levels among subject subgroups in Asian (all were Chinese) (A), non-Hispanic Caucasian (B), non-Hispanic African American (C) and Hispanic (D) subjects. uL-selectin in LN patients correlated with AI (E) and CI (F) by Spearman correlation analysis in Chinese subjects. (G) Correlation matrix for comparison of uL-selectin and conventional metrics (serum C3, C4, anti-dsDNA and 24h proteinuria) with renal pathology AI, CI and their component attributes. Urinary L-selectin levels were compared in active LN patients at the endpoints of follow up and those at baseline in the remission group (CRR+PRR) (H) and the non-remission group (NR) (I, J) The forest plot summarizes results from univariate and multivariate logistic regression analysis for high renal pathology CI (CI>3)
Demographic and clinical characteristics of study subjects from the Chinese cohort (n=255)
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