Abstract
Given the urgent need for non-invasive biomarkers of LN, we aim to identify novel urinary biomarkers that facilitate diagnosis, assessment of disease activity and prediction of treatment response in a retrospective SLE cohort. A total of 154 SLE patients and 55 healthy controls were enrolled, among whom 73 were active LN patients. We measured renal activity by renal SLEDAI. The treatment response of the active LN patients who finished 6-month induction therapy was assessed based on the American College of Rheumatology response criteria. The expression levels of 10 urinary biomarkers (UBMs): β2-MG, calbindin D, cystatin C, IL-18, KIM-1, MCP-1, nephrin, NGAL, VCAM-1, and VDBP were tested using Luminex high-throughput proteomics technology. All but urinary nephrin levels were significantly increased in active LN compared to healthy controls. uCystatinC, uMCP-1, uKIM-1 levels were significantly higher in active LN group compared to inactive LN group. Correlation analysis revealed positive correlation between uCystatinC, uKIM-1, uMCP-1, uNGAL, uVDBP and RSLEDAI score. In renal pathology, uCystatinC, uKIM-1, uVCAM-1, and uVDBP positively correlated with activity index (AI) while uVCAM-1 positively correlated with chronicity index (CI). Moreover, the combination of uVCAM-1, uCystatinC, uKIM-1 discriminated proliferative LN from membranous LN with an AUC of 0.80 (95%CI: 0.69-0.90). Most importantly, baseline uNGAL demonstrated good prediction ability to discriminate responders from non-responders in active LN patients after 6-month induction therapy. Using a multiplex bead technique, we have identified the combination of uVCAM-1, uCystatinC, uKIM-1 as a biomarker panel to reflect renal pathology and NGAL as a promising urinary biomarker to both reflect disease activity and predict treatment response.
Highlights
ObjectivesGiven the urgent need for non-invasive biomarkers of Lupus nephritis (LN), we aim to identify novel urinary biomarkers that facilitate diagnosis, assessment of disease activity and prediction of treatment response in a retrospective Systemic lupus erythematosus (SLE) cohort
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease with unknown etiology
In this retrospective cohort study, a total of 154 SLE patients (94% women) above 18 years of age from Renji Hospital, Shanghai Jiao Tong University School of Medicine were recruited from August 1, 2016 to August 1, 2018, including 73 active Lupus nephritis (LN), 32 inactive LN, 49 non-renal SLE. 55 age and gender matched healthy individuals were recruited as controls
Summary
Given the urgent need for non-invasive biomarkers of LN, we aim to identify novel urinary biomarkers that facilitate diagnosis, assessment of disease activity and prediction of treatment response in a retrospective SLE cohort. We aim to use a more sensitive multiplex technology to simultaneously quantitate ten potential UBMs and establish the potential role of urine protein biomarker panel in reflecting disease activity and predicting treatment response in LN patients
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