Soluble IL-2R Test: A Diagnostic Marker for Immune Activation and Disease
The soluble Interleukin-2 Receptor (sIL-2R) test is a blood test that measures levels of circulating IL-2 receptors released during T-cell activation and is a valuable diagnostic marker for various immune-mediated diseases, particularly hemophagocytic lymphohistiocytosis (HLH), sarcoidosis, and lymphoid malignancies.
What is sIL-2R?
Soluble IL-2R (also called sCD25) is the released form of the interleukin-2 receptor that appears in blood when T-cells are activated. It serves as a biomarker of immune system activation with several important characteristics:
- Released upon T-cell activation in various immune and inflammatory conditions
- Normal serum levels in healthy individuals are typically around 238-338 U/mL 1, 2
- Cerebrospinal fluid (CSF) levels are normally much lower (approximately 15 U/mL) 3
Clinical Applications
Hemophagocytic Lymphohistiocytosis (HLH)
sIL-2R is a key diagnostic criterion for HLH:
- Levels ≥ 2400 U/mL are part of the formal HLH-2004 diagnostic criteria 4
- Superior diagnostic performance compared to ferritin with an area under the curve of 0.90 (vs. 0.78 for ferritin) 4
- Essential component of HLH workup along with ferritin, triglycerides, fibrinogen, and evidence of hemophagocytosis 4
Sarcoidosis
- Elevated serum sIL-2R, along with ACE and lysozyme levels, are useful diagnostic tools for sarcoidosis 4
- Higher levels correlate with more aggressive disease and multiple-organ involvement 4
- Used to evaluate disease activity and monitor treatment response 2
Lymphoid Malignancies
Significantly elevated in patients with hematological malignancies compared to solid tumors or healthy controls 5, 6
Levels correlate with tumor burden and disease activity 1
Particularly useful in:
- Undifferentiated and lymphoblastic lymphomas
- Non-Hodgkin's lymphoma
- Acute leukemias
- Multiple myeloma
Prognostic value: Higher levels correlate with poorer disease-free interval and survival in lymphomas 1
CSF sIL-2R can indicate CNS involvement in hematological malignancies 3
Other Immune-Mediated Conditions
sIL-2R is also valuable in:
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Juvenile idiopathic arthritis
- Adult-onset Still's disease
- ANCA-associated vasculitis
- IgG4-related disease 2
Interpretation Guidelines
- Lymphoma screening: At levels >1,946 U/mL, specificity reaches 93% for lymphoma diagnosis 6
- HLH diagnosis: Levels ≥2,400 U/mL support diagnosis when combined with other criteria 4
- Acute pancreatitis: Elevated levels (peaking around day 7) correlate with multiple organ complications 4, 7
- COVID-19 hyperinflammation: Elevated levels indicate hyperinflammation requiring immunomodulatory therapy 4
Clinical Pearls and Pitfalls
- Not disease-specific: While highly sensitive for immune activation, sIL-2R is not specific to any single condition
- Context matters: Interpretation requires correlation with clinical presentation and other laboratory findings
- False positives: Can be elevated in non-lymphoid solid tumors, severe infections, and inflammatory conditions 2, 5
- Age and other factors: Age >46 years and elevated LDH may increase likelihood of lymphoma when sIL-2R is elevated 6
- Treatment monitoring: Serial measurements can help monitor disease activity and treatment response 1, 2
Testing Considerations
- Sample type: Typically measured in serum, but can also be measured in CSF when CNS involvement is suspected
- Method: Usually measured by enzyme-linked immunosorbent assay (ELISA)
- Timing: Levels may fluctuate with disease activity, so timing of collection is important for interpretation
- Reference ranges: May vary between laboratories, requiring familiarity with local reference values
The sIL-2R test is a valuable tool in the diagnostic workup of suspected immune-mediated diseases, particularly when integrated with other clinical and laboratory findings to guide diagnosis and treatment decisions.