title: Monomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured by ELISA as biomarkers in arthritis.
abstract: BACKGROUND
  SELDI-TOF mass spectrometry (MS) is a high-throughput proteomic approach with potential for identifying novel forms of serum biomarkers of arthritis.
  
  
  METHODS
  We used SELDI-TOF MS to analyze serum samples from patients with various forms of inflammatory arthritis. Several protein profiles were collected on different Bio-Rad Laboratories ProteinChip arrays (CM10 and IMAC-Cu(2+)) and were evaluated statistically to select potential biomarkers.
  
  
  RESULTS
  SELDI-TOF MS analyses identified several calgranulin proteins [S100A8 (calgranulin A), S100A9 (calgranulin B), S100A9*, and S100A12 (calgranulin C)], serum amyloid A (SAA), SAA des-Arg (SAA-R), and SAA des-Arg/des-Ser (SAA-RS) as biomarkers and confirmed the results with other techniques, such as western blotting, immunoprecipitation, and nano-LC-MS/MS. The S100 proteins were all able to significantly differentiate samples from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from those of patients with inflammatory bowel diseases used as an inflammatory control (IC) group, whereas the SAA, SAA-R, and SAA-RS proteins were not, with the exception of AS. The 4 S100 proteins were coproduced in all of the pathologies and were significantly correlated with the plasma calprotectin concentration; however, these S100 proteins were correlated with the SAA peak intensities only in the RA and IC patient groups. In RA, these S100 proteins (except for S100A12) were significantly correlated with the serum concentrations of C-reactive protein, matrix metalloproteinase 3, and anti-cyclic citrullinated peptide and with the Disease Activity Score (DAS(28)).
  
  
  CONCLUSIONS
  The SELDI-TOF MS technology is a powerful approach for analyzing the status of monomeric, truncated, or posttranslationally modified forms of arthritis biomarkers, such as the S100A8, S100A9, S100A12, and SAA proteins. The fact that the SELDI-TOF MS data were correlated with results obtained with the classic calprotectin ELISA test supports the reliability of this new proteomic technique.
authors.affiliation: Laboratory of Rheumatology, GIGA Research, CHU, University of Liège, Liège, Belgium. ddeseny@chu.ulg.ac.de
authors.forename: Dominique
authors.initials: D
authors.lastname: de Seny
authors.forename: Marianne
authors.initials: M
authors.lastname: Fillet
authors.forename: Clio
authors.initials: C
authors.lastname: Ribbens
authors.forename: Raphaël
authors.initials: R
authors.lastname: Marée
authors.forename: Marie-Alice
authors.initials: MA
authors.lastname: Meuwis
authors.forename: Laurence
authors.initials: L
authors.lastname: Lutteri
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Chapelle
authors.forename: Louis
authors.initials: L
authors.lastname: Wehenkel
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Merville
authors.forename: Michel
authors.initials: M
authors.lastname: Malaise
mesh_terms: D000328:Adult; D000368:Aged; D001168:Arthritis / Q000175:diagnosis* / Q000209:etiology; D001172:Arthritis, Rheumatoid / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D040501:Calgranulin A / Q000097:blood; D040502:Calgranulin B / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000150:complications; D009418:S100 Proteins / Q000097:blood; D000067616:S100A12 Protein; D000685:Serum Amyloid A Protein / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013167:Spondylitis, Ankylosing / Q000150:complications
chemical_list: D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D039841:Leukocyte L1 Antigen Complex; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D000685:Serum Amyloid A Protein