A step forward in pediatric hemophagocytic lymphohistiocytosis and autoimmune disease: pediatric reference interval for serum soluble IL-2 receptor and soluble CD163.

Objectives: Hemophagocytic lymphohistiocytosis (HLH) is a severe condition requiring timely diagnosis to initiate immunomodulatory therapy. Soluble interleukin-2 receptor (sIL-2R) and soluble CD163 (sCD163) are biomarkers crucial for making this diagnosis. This study aims to establish pediatric reference intervals (RIs) for serum concentrations of sIL-2R and sCD163, and to evaluate the pre-analytic stability of sIL-2R.

Methods: Serum samples from 243 healthy children (aged 0-18 years) were analyzed to determine RIs for sIL-2R and sCD163. Samples were processed according to stringent pre-analytic protocols, with additional stability studies evaluating sIL-2R under various conditions, including temperature fluctuations and freeze-thaw cycles. The concentration of sCD163 was additionally determined in a protein reference material. RIs were calculated using non-parametric quantile regression, and subgroups were analyzed for potential partitioning by age, sex, and inflammation status (C-reactive protein (CRP) >8 mg/L).

Results: Discrete and continuous RIs were established for serum sIL-2R and sCD163 in healthy children, with distinct age-dependent variations observed for sIL-2R. Stability studies confirmed sIL-2R's robustness under common pre-analytic conditions. Results were consistent across samples obtained from general practitioners and hospital clinics, enhancing their transferability.

Conclusions: This study provides comprehensive pediatric RIs for serum sIL-2R and sCD163 to support clinical decision-making in HLH and related inflammatory disorders. The stability of both sIL-2R and sCD163 under diverse conditions supports their reliable use in clinical settings. These findings may facilitate broader clinical implementation, pending on local validation and standardization.