title: Calprotectin (S100A8/A9) and S100A12 are associated with measures of disease activity in a longitudinal study of patients with rheumatoid arthritis treated with infliximab.
abstract: OBJECTIVE
  The pro-inflammatory proteins calprotectin (a heterocomplex of S100A8/A9) and S100A12 have been associated with disease activity in rheumatoid arthritis (RA). The aim of this study was to compare their potential as biomarkers in a prospective study of RA patients starting with infliximab as their first biological disease-modifying anti-rheumatic drug (DMARD).
  
  
  METHODS
  Thirty-nine RA patients were examined and serum samples collected when starting with infliximab and after 3, 6, and 12 months. Calprotectin and S100A12 were analysed by enzyme-linked immunosorbent assays (ELISAs) and, together with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), measured at all time points. A disease activity score of 28 joints (DAS28) was calculated. Radiographs of the hands, wrists, and feet were taken at baseline and after 3 years, and assessed according to the modified Sharp/van der Heijde (SvH) score. Responsiveness was evaluated according to the European League of Associations for Rheumatology (EULAR) response criteria based on 28 joints.
  
  
  RESULTS
  Both S100 proteins were significantly higher in seropositive than in seronegative patients (p = 0.01). Calprotectin correlated significantly with CRP (ρ = 0.51-0.75), ESR (ρ = 0.32-0.52), and DAS28 (ρ = 0.32-0.62). S100A12 correlated with calprotectin (ρ = 0.62-0.77) and CRP (ρ = 0.32-0.63). The S100 proteins, and especially calprotectin (ρ = 0.23-0.39), showed weak associations with radiographic progression, unlike CRP/ESR. None of the S100 proteins could predict responsiveness.
  
  
  CONCLUSIONS
  Calprotectin showed the strongest correlation with measures of disease activity and may be better than S100A12 when evaluating disease activity in RA patients. More extensive studies are needed to further compare the predictive value of the S100 proteins relative to radiographic progression.
authors.affiliation: a Broegelmann Research Laboratory, Department of Clinical Science , University of Bergen , Bergen , Norway.|b Department of Rheumatology , Haukeland University Hospital , Bergen , Norway.
authors.forename: H H
authors.initials: HH
authors.lastname: Nordal
authors.affiliation: a Broegelmann Research Laboratory, Department of Clinical Science , University of Bergen , Bergen , Norway.|b Department of Rheumatology , Haukeland University Hospital , Bergen , Norway.
authors.forename: J G
authors.initials: JG
authors.lastname: Brun
authors.affiliation: c Department of Radiology , Haukeland University Hospital and Unilabs Røntgen Bergen , Bergen , Norway.
authors.forename: M
authors.initials: M
authors.lastname: Hordvik
authors.affiliation: a Broegelmann Research Laboratory, Department of Clinical Science , University of Bergen , Bergen , Norway.
authors.forename: M
authors.initials: M
authors.lastname: Eidsheim
authors.affiliation: a Broegelmann Research Laboratory, Department of Clinical Science , University of Bergen , Bergen , Norway.|b Department of Rheumatology , Haukeland University Hospital , Bergen , Norway.
authors.forename: R
authors.initials: R
authors.lastname: Jonsson
authors.affiliation: b Department of Rheumatology , Haukeland University Hospital , Bergen , Norway.
authors.forename: A-K
authors.initials: AK
authors.lastname: Halse
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000276:immunology; D040501:Calgranulin A / Q000097:blood*; D040502:Calgranulin B / Q000097:blood*; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D033023:Foot Joints / Q000000981:diagnostic imaging; D005938:Glucocorticoids / Q000627:therapeutic use; D050823:Hand Joints / Q000000981:diagnostic imaging; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D039841:Leukocyte L1 Antigen Complex / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011239:Prednisolone / Q000627:therapeutic use; D011446:Prospective Studies; D011859:Radiography; D012217:Rheumatoid Factor / Q000276:immunology; D000067616:S100A12 Protein / Q000097:blood*; D012720:Severity of Illness Index; D014955:Wrist Joint / Q000000981:diagnostic imaging; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D005938:Glucocorticoids; D039841:Leukocyte L1 Antigen Complex; D010456:Peptides, Cyclic; D000067616:S100A12 Protein; C090441:S100A12 protein, human; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; D011239:Prednisolone; D000069285:Infliximab; D008727:Methotrexate