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

Arthritis Rheum. 2007 Mar;56(3):965-71. doi: 10.1002/art.22416.


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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, CD / blood*
  • Antigens, Differentiation, Myelomonocytic / blood*
  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / complications*
  • Arthritis, Juvenile / diagnosis*
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Female
  • Ferritins / blood
  • Humans
  • Interleukin-2 Receptor alpha Subunit / blood*
  • Macrophage Activation*
  • Macrophages / pathology
  • Male
  • Prospective Studies
  • Receptors, Cell Surface / blood*
  • Syndrome
  • T-Lymphocytes / pathology


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Cell Surface
  • Ferritins