title: S100A12 is a novel molecular marker differentiating systemic-onset juvenile idiopathic arthritis from other causes of fever of unknown origin.
abstract: OBJECTIVE
  Fever of unknown origin (FUO) in children presents a diagnostic challenge. The differential diagnosis includes systemic-onset juvenile idiopathic arthritis (JIA), an autoinflammatory syndrome associated with activation of phagocytic cells that, at presentation, is difficult to differentiate from severe systemic infections. The aim of this study was to investigate whether serum concentrations of the phagocytic proinflammatory protein S100A12 may help in deciding whether to treat patients with FUO with antibiotics or immunosuppressive agents.
  
  
  METHODS
  Serum samples were obtained from 45 healthy control subjects and from 240 patients (60 with systemic-onset JIA, 17 with familial Mediterranean fever [FMF], 18 with neonatal-onset multisystem inflammatory disease [NOMID], 17 with Muckle-Wells syndrome [MWS], 40 with acute lymphoblastic leukemia [ALL], 5 with acute myeloblastic leukemia [AML], and 83 with systemic infections). All samples were collected at the time of presentation, before the initiation of any treatment, and concentrations of S100A12 were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The mean +/- 95% confidence interval serum levels of S100A12 were as follows: in patients with JIA, 7,190 +/- 2,690 ng/ml; in patients with FMF, 6,720 +/- 4,960 ng/ml; in patients with NOMID, 720 +/- 450 ng/ml; in patients with MWS, 150 +/- 60 ng/ml; in patients with infections, 470 +/- 160 ng/ml; in patients with ALL, 130 +/- 80 ng/ml; in patients with AML, 45 +/- 60 ng/ml; in healthy control subjects, 50 +/- 10 ng/ml. The sensitivity and specificity of S100A12 to distinguish between systemic-onset JIA and infections were 66% and 94%, respectively.
  
  
  CONCLUSIONS
  S100A12, a marker of granulocyte activation, is highly overexpressed in patients with systemic-onset JIA or FMF, which may point to as-yet unknown common inflammatory mechanisms in these diseases. The measurement of S100A12 serum levels may provide a valuable diagnostic tool in the evaluation of FUO.
authors.affiliation: University Hospital Muenster, Muenster, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Wittkowski
authors.forename: Michael
authors.initials: M
authors.lastname: Frosch
authors.forename: Nico
authors.initials: N
authors.lastname: Wulffraat
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
authors.forename: Tilmann
authors.initials: T
authors.lastname: Kallinich
authors.forename: Jasmin
authors.initials: J
authors.lastname: Kuemmerle-Deschner
authors.forename: Michael C
authors.initials: MC
authors.lastname: Frühwald
authors.forename: Sandra
authors.initials: S
authors.lastname: Dassmann
authors.forename: Tuyet-Hang
authors.initials: TH
authors.lastname: Pham
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Dirk
authors.initials: D
authors.lastname: Foell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001171:Arthritis, Juvenile / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D010505:Familial Mediterranean Fever / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D005260:Female; D005335:Fever of Unknown Origin / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007223:Infant; D007239:Infections / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D009418:S100 Proteins / Q000097:blood*; D000067616:S100A12 Protein; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human