Urine Peptidomic and Targeted Plasma Protein Analyses in the Diagnosis and Monitoring of Systemic Juvenile Idiopathic Arthritis

Clinical Proteomics

Jane L. Park³  Claudia Macaubas³  Chris Xiao³  James Schilling³  Kenneth Lau³  Viorica Lopez-Avila¹  Xuefeng B. Ling³  Harvey Cohen³  Diana Milojevic⁴  Chetan Deshpande³  Jane C. Burns²  John Kanegaye²  Elizabeth D. Mellins³ 

[1] Agilent Technologies, Santa Clara, USAAgilent Technologies, Santa Clara, USAAgilent Technologies, Santa Clara, USA;UCSD, La Jolla, USAUCSD, La Jolla, USAUCSD, La Jolla, USA;Department of Pediatrics, Stanford University, Stanford, USADepartment of Pediatrics, Stanford University, Stanford, USADepartment of Pediatrics, Stanford University, Stanford, USA;UCSF, San Francisco, USAUCSF, San Francisco, USAUCSF, San Francisco, USA

关键词: Urine;    Arthritis;    Inflammation;    Proteomics;    Antibody;    Biomarker;    Predictor;   

DOI  :  10.1007/s12014-010-9058-8

来源: Humana Press Inc

【 摘 要 】

Abstract

Purpose

Systemic juvenile idiopathic arthritis is a chronic pediatric disease. The initial clinical presentation can mimic other pediatric inflammatory conditions, which often leads to significant delays in diagnosis and appropriate therapy. SJIA biomarker development is an unmet diagnostic/prognostic need to prevent disease complications.

Experimental Design

We profiled the urine peptidome to analyze a set of 102 urine samples, from patients with SJIA, Kawasaki disease (KD), febrile illnesses (FI), and healthy controls. A set of 91 plasma samples, from SJIA flare and quiescent patients, were profiled using a customized antibody array against 43 proteins known to be involved in inflammatory and protein catabolic processes.

Results

We identified a 17-urine-peptide biomarker panel that could effectively discriminate SJIA patients at active, quiescent, and remission disease states, and patients with active SJIA from confounding conditions including KD and FI. Targeted sequencing of these peptides revealed that they fall into several tight clusters from seven different proteins, suggesting disease-specific proteolytic activities. The antibody array plasma profiling identified an SJIA plasma flare signature consisting of tissue inhibitor of metalloproteinase-1 (TIMP1), interleukin (IL)-18, regulated upon activation, normal T cell expressed and secreted (RANTES), P-Selectin, MMP9, and L-Selectin.

Conclusions and Clinical Relevance

The urine peptidomic and plasma protein analyses have the potential to improve SJIA care and suggest that SJIA urine peptide biomarkers may be an outcome of inflammation-driven effects on catabolic pathways operating at multiple sites.

【 授权许可】

Unknown