Interleukin-2 Receptor Alpha Chain (IL-2Ra/CD25), Soluble
Interleukin-2 Receptor Alpha Chain (IL-2Ra/CD25), Soluble
This test is used to diagnose hemophagocytic lymphohistiocytosis (HLH) in symptomatic patients, assess prognosis in patients with lymphoma, and monitor disease activity and therapeutic response in patients with sarcoidosis.
Test Summary
Interleukin-2 Receptor Alpha Chain (IL-2Ra/CD25), Soluble
Test code: 34298
Clinical use
- Diagnose hemophagocytic lymphohistiocytosis (HLH) in symptomatic patients
- Assess prognosis in patients with lymphoma
- Monitor disease activity and therapeutic response in patients with sarcoidosis
Clinical background
Elevated levels of soluble interleukin-2 receptor α-chain (IL-2Ra/CD25) are detected in the serum of patients with a broad spectrum of conditions associated with T- or B-cell immune activation, including infections, inflammation, lymphomas, and autoimmune disease.1 For some of these conditions, measurement of IL-2Ra/CD25 levels is used in diagnosis, prognosis, and monitoring response to therapy.
Elevated levels of soluble IL-2Ra/CD25 are 1 of the 8 nonmolecular diagnostic criteria for HLH in children (Table). A diagnosis of HLH is made if 5 of 8 of these criteria are met.2 The criteria are also commonly used in adults, although the test may be less specific for HLH in adults than in children.3
Table. Diagnostic Criteria for HLH in Children
Criterion2 |
Requirement |
Cytopenia |
Affecting ≥2 of 3 lineages in the peripheral blood |
Fever |
Present |
Hemophagocytosis |
In bone marrow, spleen, or lymph nodes (nonmalignant) |
Hypertriglyceridemia and/or hypofibrinogenemia |
|
IL-2Ra/CD25 |
≥2,400 U/mLa |
Natural killer cell activity |
Low or absent |
Serum ferritin |
≥500 μg/L |
Splenomegaly |
Present |
| a | This assay reports results in pg/mL, and a direct comparison with this cutoff is not possible.4 However, a comparable cutoff of 20,000 pg/mL has been suggested for enzyme-linked immunosorbent assay (ELISA) results.1 |
Elevated levels of soluble IL-2Ra/CD25 may also have clinical and prognostic significance in patients with various lymphomas. For example, in non-Hodgkin lymphoma, elevated levels correlate with a poor prognosis.1 In T-cell lymphoma, high levels suggest a short median survival time.1 In B-cell lymphoma, high levels are associated with tumor load and poor progression-free survival.1
Soluble IL-2Ra/CD25 levels may also provide a rapid and reliable measure of disease activity and response to therapy for several conditions, including transplantation rejection,5 infections,1,6 autoimmune disease.1,6 For example, soluble IL-2Ra/CD25 levels may be used to monitor therapeutic response in patients with sarcoidosis,1,6,7 although conflicting conclusions regarding the strength of the association with disease activity have been reported.6 For patients with sarcoidosis specifically affecting cardiac tissue, recent studies suggest that elevated soluble IL-2Ra/CD25 levels reflect disease activity and poor prognosis.8,9 Currently, soluble IL-2Ra/CD25 testing has not been included in sarcoidosis guidelines.10
Individuals suitable for testing
- Individuals with suspected HLH (see Table)
- Individuals with lymphoma
- Individuals with sarcoidosis
Method
- Automated microfluidics immunoassay
- Reportable range: 16-400,000 pg/mL
Interpretive information
Elevated levels of IL-2Ra/CD25 (Table) in serum are supportive of a diagnosis of HLH in a symptomatic patient.
Elevated levels have also been associated with a poor prognosis for lymphoma patients.1 An elevation can be identified by comparing a patient specimen's value with the reference range. Elevated levels have also been associated with a poor prognosis for lymphoma patients.1 Results from this assay are considered elevated if above the 97.5th percentile value (determined from 120 apparently healthy adults 18 to 65 years old not taking over-the-counter or prescription medications, including oral contraceptives).
Among individuals with sarcoidosis, elevated levels may be associated with acute or active disease, disease progression in the absence of treatment, or the need for long-term therapy.6 On the other hand, decreased levels relative to a highly elevated baseline (eg, >3,000 pg/mL reduction after 6 months of treatment)7 may reflect therapeutic response.6 Note: not all studies support these interpretations.6
References
- Damoiseaux J. The IL-2 – IL-2 receptor pathway in health and disease: the role of the soluble IL-2 receptor. Clin Immunol. 2020;218:108515. doi:10.1016/j.clim.2020.108515
- Henter JI, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatric Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039
- Hayden A, Lin M, Park S, et al. Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH. Blood Adv. 2017;1(26):2529-2534. doi:10.1182/bloodadvances.2017012310
- Bilston L, Croden J, Taparia M, et al. Validation of the HScore and the HLH-2004 diagnostic criteria for the diagnosis of hemophagocytic lymphohistiocytosis in a multicenter cohort. Eur J Haematol. 2022;109(2):129-137. doi:10.1111/ejh.13779
- Lia G, Giaccone L, Leone S, et al. Biomarkers for early complications of endothelial origin after allogeneic hematopoietic stem cell transplantation: do they have a potential clinical role? Front Immunol. 2021;12:641427. doi:10.3389/fimmu.2021.641427
- Ramos-Casals M, Retamozo S, Sisó-Almirall A, et al. Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis. Expert Rev Clin Immunol. 2019;15(4):391-405. doi:10.1080/1744666X.2019.1568240
- Schimmelpennink MC, Vorselaars ADM, van Beek FT, et al. Efficacy and safety of infliximab biosimilar Inflectra® in severe sarcoidosis. Respir Med. 2018;138S:S7-S13. doi:10.1016/j.rmed.2018.02.009
- Kobayashi Y, Sato T, Nagai T, et al. Association of high serum soluble interleukin 2 receptor levels with risk of adverse events in cardiac sarcoidosis. ESC Heart Fail. 2021;8(6):5282-5292. doi:10.1002/ehf2.13614
- Reithmann C, Min S, Kling T, et al. Role of serum soluble interleukin 2-receptor in the evaluation of myocardial inflammation in patients with cardiac sarcoidosis and ventricular arrhythmias. J Interv Card Electrophysiol. 2022;10.1007/s10840-022-01271-4. doi:10.1007/s10840-022-01271-4
- Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and detection of sarcoidosis: an official American Thoracic Society clinical practice guideline. Am J Resp Crit Care Med. 2020;201(8):e26-e51. doi:10.1164/rccm.202002-0251st
Content reviewed 11/2022
This test is used to diagnose hemophagocytic lymphohistiocytosis (HLH) in symptomatic patients, assess prognosis in patients with lymphoma, and monitor disease activity and therapeutic response in patients with sarcoidosis.
Test Summary
Interleukin-2 Receptor Alpha Chain (IL-2Ra/CD25), Soluble
Test code: 34298
Clinical use
- Diagnose hemophagocytic lymphohistiocytosis (HLH) in symptomatic patients
- Assess prognosis in patients with lymphoma
- Monitor disease activity and therapeutic response in patients with sarcoidosis
Clinical background
Elevated levels of soluble interleukin-2 receptor α-chain (IL-2Ra/CD25) are detected in the serum of patients with a broad spectrum of conditions associated with T- or B-cell immune activation, including infections, inflammation, lymphomas, and autoimmune disease.1 For some of these conditions, measurement of IL-2Ra/CD25 levels is used in diagnosis, prognosis, and monitoring response to therapy.
Elevated levels of soluble IL-2Ra/CD25 are 1 of the 8 nonmolecular diagnostic criteria for HLH in children (Table). A diagnosis of HLH is made if 5 of 8 of these criteria are met.2 The criteria are also commonly used in adults, although the test may be less specific for HLH in adults than in children.3
Table. Diagnostic Criteria for HLH in Children
Criterion2 |
Requirement |
Cytopenia |
Affecting ≥2 of 3 lineages in the peripheral blood |
Fever |
Present |
Hemophagocytosis |
In bone marrow, spleen, or lymph nodes (nonmalignant) |
Hypertriglyceridemia and/or hypofibrinogenemia |
|
IL-2Ra/CD25 |
≥2,400 U/mLa |
Natural killer cell activity |
Low or absent |
Serum ferritin |
≥500 μg/L |
Splenomegaly |
Present |
| a | This assay reports results in pg/mL, and a direct comparison with this cutoff is not possible.4 However, a comparable cutoff of 20,000 pg/mL has been suggested for enzyme-linked immunosorbent assay (ELISA) results.1 |
Elevated levels of soluble IL-2Ra/CD25 may also have clinical and prognostic significance in patients with various lymphomas. For example, in non-Hodgkin lymphoma, elevated levels correlate with a poor prognosis.1 In T-cell lymphoma, high levels suggest a short median survival time.1 In B-cell lymphoma, high levels are associated with tumor load and poor progression-free survival.1
Soluble IL-2Ra/CD25 levels may also provide a rapid and reliable measure of disease activity and response to therapy for several conditions, including transplantation rejection,5 infections,1,6 autoimmune disease.1,6 For example, soluble IL-2Ra/CD25 levels may be used to monitor therapeutic response in patients with sarcoidosis,1,6,7 although conflicting conclusions regarding the strength of the association with disease activity have been reported.6 For patients with sarcoidosis specifically affecting cardiac tissue, recent studies suggest that elevated soluble IL-2Ra/CD25 levels reflect disease activity and poor prognosis.8,9 Currently, soluble IL-2Ra/CD25 testing has not been included in sarcoidosis guidelines.10
Individuals suitable for testing
- Individuals with suspected HLH (see Table)
- Individuals with lymphoma
- Individuals with sarcoidosis
Method
- Automated microfluidics immunoassay
- Reportable range: 16-400,000 pg/mL
Interpretive information
Elevated levels of IL-2Ra/CD25 (Table) in serum are supportive of a diagnosis of HLH in a symptomatic patient.
Elevated levels have also been associated with a poor prognosis for lymphoma patients.1 An elevation can be identified by comparing a patient specimen's value with the reference range. Elevated levels have also been associated with a poor prognosis for lymphoma patients.1 Results from this assay are considered elevated if above the 97.5th percentile value (determined from 120 apparently healthy adults 18 to 65 years old not taking over-the-counter or prescription medications, including oral contraceptives).
Among individuals with sarcoidosis, elevated levels may be associated with acute or active disease, disease progression in the absence of treatment, or the need for long-term therapy.6 On the other hand, decreased levels relative to a highly elevated baseline (eg, >3,000 pg/mL reduction after 6 months of treatment)7 may reflect therapeutic response.6 Note: not all studies support these interpretations.6
References
- Damoiseaux J. The IL-2 – IL-2 receptor pathway in health and disease: the role of the soluble IL-2 receptor. Clin Immunol. 2020;218:108515. doi:10.1016/j.clim.2020.108515
- Henter JI, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatric Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039
- Hayden A, Lin M, Park S, et al. Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH. Blood Adv. 2017;1(26):2529-2534. doi:10.1182/bloodadvances.2017012310
- Bilston L, Croden J, Taparia M, et al. Validation of the HScore and the HLH-2004 diagnostic criteria for the diagnosis of hemophagocytic lymphohistiocytosis in a multicenter cohort. Eur J Haematol. 2022;109(2):129-137. doi:10.1111/ejh.13779
- Lia G, Giaccone L, Leone S, et al. Biomarkers for early complications of endothelial origin after allogeneic hematopoietic stem cell transplantation: do they have a potential clinical role? Front Immunol. 2021;12:641427. doi:10.3389/fimmu.2021.641427
- Ramos-Casals M, Retamozo S, Sisó-Almirall A, et al. Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis. Expert Rev Clin Immunol. 2019;15(4):391-405. doi:10.1080/1744666X.2019.1568240
- Schimmelpennink MC, Vorselaars ADM, van Beek FT, et al. Efficacy and safety of infliximab biosimilar Inflectra® in severe sarcoidosis. Respir Med. 2018;138S:S7-S13. doi:10.1016/j.rmed.2018.02.009
- Kobayashi Y, Sato T, Nagai T, et al. Association of high serum soluble interleukin 2 receptor levels with risk of adverse events in cardiac sarcoidosis. ESC Heart Fail. 2021;8(6):5282-5292. doi:10.1002/ehf2.13614
- Reithmann C, Min S, Kling T, et al. Role of serum soluble interleukin 2-receptor in the evaluation of myocardial inflammation in patients with cardiac sarcoidosis and ventricular arrhythmias. J Interv Card Electrophysiol. 2022;10.1007/s10840-022-01271-4. doi:10.1007/s10840-022-01271-4
- Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and detection of sarcoidosis: an official American Thoracic Society clinical practice guideline. Am J Resp Crit Care Med. 2020;201(8):e26-e51. doi:10.1164/rccm.202002-0251st
Content reviewed 11/2022