International validation of a urinary biomarker pa

Authors: Eve Mary Dorothy Smith Andrea Lyn Jorgensen Angela Midgley Louise Oni Beatrice Goilav Chaim Putterman Dawn Wahezi Tamar Rubinstein Diana Ekdawy Rachel Corkhill Caroline Ann Jones Stephen David Marks Paul Newland Clarissa Pilkington Kjell Tullus Michael William Beresford

Publish Date: 2016/09/03

Volume: 32, Issue: 2, Pages: 283-295

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Abstract

Conventional markers of juvenileonset 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 cohortsNovel urinary biomarkers namely vascular cell adhesion molecule1 VCAM1 monocyte chemoattractant protein 1 MCP1 lipocalinlike prostaglandin D synthase LPGDS transferrin TF ceruloplasmin alpha1acid glycoprotein AGP and neutrophil gelatinaseassociated lipocalin NGAL were quantified in a crosssectional 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 accuracyA 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 VCAM1 MCP1 and LPGDS levels were significantly higher in those patients with active LN than in nonLN patients all corrected p values p c  005 across both cohorts Urinary TF also differed between patient groups in Cohort 2 p c = 0001 Within Cohort 1 the optimal biomarker panel included AGP ceruloplasmin LPGDS and TF AUC 0920 for active LN identification These results were validated in Cohort 2 with the same markers resulting in the optimal urine biomarker panel AUC 0991Juvenileonset systemic lupus erythematosus JSLE is a lifethreatening multisystem autoimmune disease that displays a more aggressive course than adult onset SLE 1 2 3 More renal manifestations occur in childhood with up to 80  of JSLE patients developing lupus nephritis LN within the first 5 years from diagnosis 1 4 5 6 7 8 9 LN is characterised by a relapsing and remitting course requiring close surveillance and prompt treatment to prevent renal damage Worldwide the 5year renal survival rate in children with LN has been shown to vary between 44 and 94  10 11 12 13Renal histology is the gold standard for diagnosing and predicating renal prognosis in LN but only provides a snapshot of a discrete area of the kidney and is rarely repeated for monitoring purposes due to its invasive nature 14 15 Composite disease activity scores such as the British Isles Lupus Assessment Group BILAG score or the Systemic Lupus Erythematosus Disease Activity Index SELENA SLEDAI and a number of traditional clinical biomarkers can be used to assess JSLE disease activity however their role in monitoring LN within the clinic is limited 16 17 18 19Over recent years 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 protein1 MCP1 neutrophil gelatinase associated lipocalin 1 NGAL vascular cell adhesion molecule1 VCAM1 and tumour necrosislike weak inducer of apoptosis TWEAK 20 21 22 23 24 25 26 Using a proteomic approach urinary transferrin TF ceruloplasmin lipocalintype prostaglandin D synthase LPGDS alpha1acid glycoprotein AGP albumin and albumin fragments have been shown to differentiate between children with active LN and no LN 27 When assessed longitudinally LPGDS AGP and TF levels were all elevated up to 3 months before the LN flare 27

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