Abstract
BackgroundConventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts.MethodsNovel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy.ResultsA total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (pc) < 0.05] across both cohorts. Urinary TF also differed between patient groups in Cohort 2 (pc = 0.001). Within Cohort 1, the optimal biomarker panel included AGP, ceruloplasmin, LPGDS and TF (AUC 0.920 for active LN identification). These results were validated in Cohort 2, with the same markers resulting in the optimal urine biomarker panel (AUC 0.991).ConclusionIn two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an ‘excellent’ ability for accurately identifying active LN in children.
Highlights
Juvenile-onset systemic lupus erythematosus (JSLE) is a lifethreatening multi-system autoimmune disease that displays a more aggressive course than adult onset SLE [1,2,3]
This study aimed to build on previous work [22, 25,26,27, 31,32,33] by exploring the most promising candidate urinary biomarkers to date used in combination, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase associated lipocalin 1 (NGAL), ceruloplasmin, TF, lipocalin-type prostaglandin D synthase (LPGDS) and acid glycoprotein (AGP) in a paediatric cohort from the UK (UK juvenile-onset systemic lupus erythematosus (JSLE) Cohort Study), to assess which novel biomarker combinations can improve the identification of active lupus nephritis (LN)
The UK JSLE Study cohort consisted of 61 patients with JSLE, of whom 15 (25 %) were classed as JSLE with active LN (2/15 renal British Isles Lupus Assessment Group (BILAG) score = A, 13/15 = B) and 46 (75 %) as JSLE with inactive LN
Summary
Juvenile-onset systemic lupus erythematosus (JSLE) is a lifethreatening multi-system autoimmune disease that displays a more aggressive course than adult onset SLE [1,2,3]. Numerous individual novel urinary biomarkers have been investigated for monitoring LN disease activity. These have outperformed both traditional and novel serum biomarkers, including monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase associated lipocalin 1 (NGAL), vascular cell adhesion molecule-1 (VCAM-1) and tumour necrosis-like weak inducer of apoptosis (TWEAK) [20,21,22,23,24,25,26]. Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts
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