Proteomic Analyses of Autologous Chondrocyte Implantation Plasma Highlight Cartilage Acidic Protein 1 as a Candidate for Preclinical Screening

Abstract

Background: Stratification is required to ensure that only patients likely to benefit receive autologous chondrocyte implantation (ACI). It would be advantageous to identify biomarkers to predict ACI outcome that are measurable in blood, avoiding the need for an invasive synovial fluid harvest. Purpose: To assess if proteomic analyses can be used to identify novel candidate blood biomarkers in individuals who respond well or poorly to ACI. Study Design: Controlled laboratory study. Methods: Isobaric tagging for relative and absolute quantitation (iTRAQ) mass spectrometry was used to assess the proteome in plasma pooled from ACI responders (mean Lysholm improvement after ACI, 33; n = 10) or nonresponders (mean, −13; n = 10), collected at the time of surgery for cartilage harvest (stage 1) or implantation of culture-expanded chondrocytes (stage 2). An alternative proteomic method, label-free quantitation liquid chromatography–tandem mass spectrometry, was used to analyze plasma samples (majority matched to iTRAQ) individually. Differentially abundant proteins (±2.0-fold) were analyzed from both proteomic data sets, and markers of interest identified via pooled iTRAQ were validated via immunoassay of individual samples. Results: Protein differences could be detected in the plasma preoperatively between ACI responders and nonresponders (16 proteins; ≥±2.0-fold change; P