The 82-plex plasma protein signature that predicts increasing inflammation

• Published in: Scientific reports Vol. 5; no. 1; p. 14882
• Main Authors: Tepel, Martin, Beck, Hans C., Tan, Qihua, Borst, Christoffer, Rasmussen, Lars M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.10.2015; Nature Publishing Group
• Subjects: 49/47; 631/61/475/2290; 692/53/2422; 82; Adult; Aged; Bioinformatics; C-reactive protein; C-Reactive Protein - metabolism; Chromatography, Liquid; Female; Health risk assessment; Humanities and Social Sciences; Humans; Inflammation; Inflammation - blood; Inflammation - diagnosis; Kidney Transplantation; Logistic Models; Male; Metabolome; Middle Aged; multidisciplinary; Plasma; Plasma proteins; Prognosis; Prospective Studies; Proteins; Proteomes; Reclassification; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - pathology; Renal Insufficiency, Chronic - surgery; ROC Curve; Science; Tandem Mass Spectrometry
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep14882

The objective of the study was to define the specific plasma protein signature that predicts the increase of the inflammation marker C-reactive protein from index day to next-day using proteome analysis and novel bioinformatics tools. We performed a prospective study of 91 incident kidney transplant recipients and quantified 359 plasma proteins simultaneously using nano-Liquid-Chromatography-Tandem Mass-Spectrometry in individual samples and plasma C-reactive protein on the index day and the next day. Next-day C-reactive protein increased in 59 patients whereas it decreased in 32 patients. The prediction model selected and validated 82 plasma proteins which determined increased next-day C-reactive protein (area under receiver-operator-characteristics curve, 0.772; 95% confidence interval, 0.669 to 0.876; P < 0.0001). Multivariable logistic regression showed that 82-plex protein signature (P < 0.001) was associated with observed increased next-day C-reactive protein. The 82-plex protein signature outperformed routine clinical procedures. The category-free net reclassification index improved with 82-plex plasma protein signature (total net reclassification index, 88.3%). Using the 82-plex plasma protein signature increased net reclassification index with a clinical meaningful 10% increase of risk mainly by the improvement of reclassification of subjects in the event group. An 82-plex plasma protein signature predicts an increase of the inflammatory marker C-reactive protein.