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Annals of Hematology

, Volume 96, Issue 8, pp 1241–1251 | Cite as

Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review

  • Molly Lin
  • Sujin Park
  • Anna Hayden
  • Dean Giustini
  • Martina Trinkaus
  • Morris Pudek
  • Andre Mattman
  • Marion Schneider
  • Luke Y.C. Chen
Review Article

Abstract

The serum-soluble interleukin-2 receptor (sIL-2r) level is considered an important diagnostic test and disease marker in hemophagocytic syndromes/hemophagocytic lymphohistiocytosis (HPS/HLH). However, this cytokine receptor is rarely measured in clinical practice and has been excluded from recent diagnostic/classification criteria such as the HScore and macrophage activation syndrome (MAS) 16. We performed a systematic scoping review of 64 articles (1975–2016) examining the clinical utility of sIL-2r in HPS/HLH. Twenty-two articles describe sIL-2r as a sensitive diagnostic marker for HLH, but only three distinct datasets actually address sensitivity. The original HLH-2004 Guidelines reported sensitivity of 93% and specificity of 100% for sIL-2r ≥ 2400, based on a pediatric dataset (n = 152) which is published for the first time in this review. Two pediatric studies reported sensitivity of 89% for sIL-2r ≥ 2400 in diagnosis of MAS complicating juvenile idiopathic arthritis (JIA) (n = 27) and 88% for secondary HLH in acute liver failure (n = 9). Twenty articles described sIL-2r as a dynamic marker of disease activity that falls with response to treatment, and 15 described high initial sIL-2r levels >10,000 U/mL as a poor prognostic marker. The ability of sIL-2r to distinguish between subtypes of HPS/HLH was inconsistent. This review confirms the importance of soluble IL-2r as a diagnostic and disease marker in HPS/HLH, but also reveals the need for more primary data about its performance characteristics, particularly in adults. More emphasis should be made in including this simple, inexpensive test in clinical practice and studies of HPS/HLH.

Keywords

Hemophagocytic lymphohistiocytosis Hemophagocytic syndrome Macrophage activation syndrome Soluble interleukin-2 receptor Interleukin-2 receptor alpha subunit Soluble CD25 

Abbreviations

FHL

Familial hemophagocytic lymphohistiocytosis

HLH

Hemophagocytic lymphohistiocytosis

HPS

Hemophagocytic syndrome (s)

IAHS

Infection-associated HPS = IAHS

JIA

Juvenile idiopathic arthritis

LAHS

Lymphoma-associated hemophagocytic syndrome

MAS

Macrophage activation syndrome

MAHS

Malignancy-associated hemophagocytic syndrome

sIL-2r

Soluble IL-2 receptor

sILRDC

Soluble IL-2 receptor diagnostic criterion ≥2400 U/mL

Notes

Acknowledgements

This work was supported by the Hal Kettleson Hematology Research Fund.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2017_2993_MOESM1_ESM.doc (220 kb)
ESM 1 (DOC 219 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Molly Lin
    • 1
  • Sujin Park
    • 1
  • Anna Hayden
    • 1
  • Dean Giustini
    • 2
  • Martina Trinkaus
    • 3
  • Morris Pudek
    • 4
  • Andre Mattman
    • 5
  • Marion Schneider
    • 6
  • Luke Y.C. Chen
    • 1
  1. 1.Division of Hematology, Department of MedicineUniversity of British ColumbiaVancouverCanada
  2. 2.Biomedical Branch LibraryUniversity of British ColumbiaVancouverCanada
  3. 3.Division of Hematology, Department of MedicineUniversity of TorontoTorontoCanada
  4. 4.Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada
  5. 5.Adult Metabolic Disease ClinicVancouver General HospitalVancouverCanada
  6. 6.Division of Experimental AnesthesiologyUniversity Hospital UlmUlmGermany

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