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

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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.

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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

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Acknowledgements

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

Author information

Author notes

  1. Molly Lin and Sujin Park contributed equally.

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, University of British Columbia, 2775 Laurel St, 10th Floor Room 10245, Vancouver, BC, V5Z 1M9, Canada

    Molly Lin, Sujin Park, Anna Hayden & Luke Y.C. Chen

  2. Biomedical Branch Library, University of British Columbia, Vancouver, Canada

    Dean Giustini

  3. Division of Hematology, Department of Medicine, University of Toronto, Toronto, Canada

    Martina Trinkaus

  4. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

    Morris Pudek

  5. Adult Metabolic Disease Clinic, Vancouver General Hospital, Vancouver, Canada

    Andre Mattman

  6. Division of Experimental Anesthesiology, University Hospital Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany

    Marion Schneider

Authors
  1. Molly Lin
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  2. Sujin Park
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  3. Anna Hayden
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  4. Dean Giustini
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  5. Martina Trinkaus
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  6. Morris Pudek
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  7. Andre Mattman
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  8. Marion Schneider
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  9. Luke Y.C. Chen
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Corresponding author

Correspondence to Luke Y.C. Chen.

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The authors declare that they have no conflict of interest.

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Lin, M., Park, S., Hayden, A. et al. Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review. Ann Hematol 96, 1241–1251 (2017). https://doi.org/10.1007/s00277-017-2993-y

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  • DOI: https://doi.org/10.1007/s00277-017-2993-y

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