Patient serum soluble interleukin-2 receptor (sIL-2r) concentration may not be a reliable diagnostic biomarker for adult secondary hemophagocytic lymphocytosis (HLH), according to results published in the European Journal of Haematology.

In adults, HLH usually occurs as a secondary condition in an inflammatory process. The investigators explained that an elevated serum sIL-2r level has been used as a diagnostic marker for HLH but that an elevated sIL-2r level can be indicative of multiple conditions.

In a retrospective analysis, a team of investigators reviewed medical records of 132 adult patients who had sent and resulted sIL-2r levels as part of a diagnostic evaluation for HLH at a tertiary urban care center. Patient records were assessed for HLH.

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Approximately half (49%) of the patients met the HLH-2004 diagnostic criteria for HLH. Patients who had HLH showed a higher mean sIL-2r level (12,942 U/mL) compared with patients without HLH (6308 U/mL; P =.00311).

No significant differences were observed between mean sIL-2r levels of HLH and non-HLH subgroups consisting of patients whose primary diagnoses were hematologic malignancy, sepsis, or rheumatologic disease.

A total of 89% of patients in the HLH group had serum sIL-2r levels that met the HLH-2004 diagnostic criterion of 2400 U/mL or higher, but 61% of patients from the non-HLH group also met this criterion.

Serum sIL-2r level was weakly correlated with HLH diagnosis (correlation coefficient, 0.253). Using the HLH-2004 serum sIL-2r threshold concentration resulted in an 89.2% sensitivity for HLH diagnosis, however, the specificity was 38.8%. Raising the sIL-2r diagnostic threshold improved specificity, although doing so reduced sensitivity and did not provide substantially greater accuracy overall.

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“In conclusion sIL-2r is a limited and fundamentally flawed test for the diagnosis of secondary HLH among adult patients,” wrote the investigators. They concluded by suggesting that diagnostic criteria for adult HLH be reexamined.


Naymagon L, Tremblay D, Troy K, Mascarenhas J. Soluble interleukin-2 receptor (sIL-2r) level is a limited test for the diagnosis of adult secondary hemophagocytic lymphohistiocytosis (HLH) [published online April 30, 2020]. Eur J Haematol. doi: 10.1111/ejh.13433