title: Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform.
abstract: BACKGROUND
  In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available.
  
  
  METHODS
  We measured, in a large ongoing cohort study (n = 574), by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD) and single-biomarker techniques (ELISA or immunoturbidimetric assay), the following biomarkers of low-grade inflammation: C-reactive protein (CRP), serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects' cardiovascular risk factors by ANOVA.
  
  
  RESULTS
  Despite that both methods ranked individuals' levels of biomarkers very similarly (Pearson's r all≥0.755) absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP), 0.711 (SAA), 0.895 (sICAM-1) and 0.858 (sVCAM-1). Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method.
  
  
  CONCLUSIONS
  Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies.
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Bas C T
authors.initials: BC
authors.lastname: van Bussel
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.forename: Marjo P H
authors.initials: MP
authors.lastname: van de Waarenburg
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: Ronald M A
authors.initials: RM
authors.lastname: Henry
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D004563:Electrochemistry / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D000685:Serum Amyloid A Protein / Q000378:metabolism; D012907:Smoking; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D000685:Serum Amyloid A Protein; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein