title: The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis.
abstract: OBJECTIVE
  Macrophage activation syndrome is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic macrophages. Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) and soluble CD163 (sCD163) may reflect the degree of activation and expansion of T cells and macrophages, respectively. This study was undertaken to assess the value of serum sIL-2Ralpha and sCD163 in diagnosing acute macrophage activation syndrome complicating systemic juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  Enzyme-linked immunosorbent assay was used to assess sIL-2Ralpha and sCD163 levels in sera from 7 patients with acute macrophage activation syndrome complicating systemic JIA and 16 patients with untreated new-onset systemic JIA. The results were correlated with clinical features of established macrophage activation syndrome, including ferritin levels.
  
  
  RESULTS
  The median level of sIL-2Ralpha in the patients with macrophage activation syndrome was 19,646 pg/ml (interquartile range [IQR] 18,128), compared with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P = 0.003). Similarly, the median level of sCD163 in patients with macrophage activation syndrome was 23,000 ng/ml (IQR 14,191), compared with 5,480 ng/ml (IQR 2,635) in patients with systemic JIA (P = 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL-2Ralpha or sCD163 were comparable with those in patients with acute macrophage activation syndrome. These patients had high inflammatory activity associated with a trend toward lower hemoglobin levels (P = 0.11), lower platelet counts, and significantly higher ferritin levels (P = 0.02). Two of these 5 patients developed overt macrophage activation syndrome several months later.
  
  
  CONCLUSIONS
  Levels of sIL-2Ralpha and sCD163 are promising diagnostic markers for macrophage activation syndrome. They may also help identify patients with subclinical macrophage activation syndrome.
authors.affiliation: Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Bleesing
authors.forename: Anne
authors.initials: A
authors.lastname: Prada
authors.forename: David M
authors.initials: DM
authors.lastname: Siegel
authors.forename: Joyce
authors.initials: J
authors.lastname: Villanueva
authors.forename: Judyann
authors.initials: J
authors.lastname: Olson
authors.forename: Norman T
authors.initials: NT
authors.lastname: Ilowite
authors.forename: Hermine I
authors.initials: HI
authors.lastname: Brunner
authors.forename: Thomas
authors.initials: T
authors.lastname: Griffin
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Graham
authors.forename: David D
authors.initials: DD
authors.lastname: Sherry
authors.forename: Murray H
authors.initials: MH
authors.lastname: Passo
authors.forename: Athimalaipet V
authors.initials: AV
authors.lastname: Ramanan
authors.forename: Alexandra
authors.initials: A
authors.lastname: Filipovich
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Grom
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D001171:Arthritis, Juvenile / Q000097:blood / Q000150:complications* / Q000175:diagnosis*; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D008262:Macrophage Activation; D008264:Macrophages / Q000473:pathology; D008297:Male; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood*; D013577:Syndrome; D013601:T-Lymphocytes / Q000473:pathology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D053645:Interleukin-2 Receptor alpha Subunit; D011956:Receptors, Cell Surface; D005293:Ferritins