Interleukin-2 Soluble Receptor α

CPT: 83520
Print Share


  • IL-2 sRα

Expected Turnaround Time

3 - 6 days

Related Documents

Specimen Requirements


Serum, frozen


0.5 mL

Minimum Volume

0.3 mL (Note: This volume does not allow for repeat testing.)


Red-top tube or gel-barrier tube


Transfer the serum into a Labcorp PP transpak frozen purple tube with screw cap (Labcorp No. 49482). Freeze immediately and maintain frozen until tested. To avoid delays in turnaround time when requesting multiple tests on frozen specimens, please submit frozen specimens for each test requested.

Storage Instructions


Stability Requirements




14 days

Freeze/thaw cycles

Stable x3

Causes for Rejection

Thawed specimen

Test Details


This test is used for the measurement of Interleukin-2 Soluble Receptor α (sIL-2Rα) levels in serum.


This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

sIL-2Rα level is only one out of eight criteria of which five have to be met to make a diagnosis. The combination of these clinical and laboratory criteria should warrant sufficient specificity. In order to reach a high specificity close to 100%, levels >10,000 U/mL are required.1

The clinical presentation of HLH can have considerable overlap with other inflammatory conditions.2 A normal or only modestly elevated sIL-2Rα, despite extremely elevated ferritin, suggests disseminated infection in the context of primary immunodeficiencies, especially in an infant.3

Although high levels of sIL-2Rα may be suggestive of sarcoidosis, there is substantial overlap in patients with other interstitial lung diseases.4


Immunochemiluminometric assay (ICMA)

Reference Interval

223−710 units/mL

Additional Information

Interleukin-2 (IL‑2) stimulates an immune response on target cells via a high affinity receptor (IL-2R) composed of alpha, beta and gamma subunits.5,6 The alpha subunit (also referred to as CD25) has no signaling capacity but confers on the receptor the ability to bind IL-2 with high-affinity.6 Signals from this receptor activate transcription factors that promote cell survival and proliferation, the two principal actions of IL-2.6 Upon antigen stimulation, T cells both produce and respond to IL-2, leading to the preferential expansion of antigen-specific clones. IL-2R is also expressed on regulatory T cells (Tregs), cells that are essential for maintaining self-tolerance, and their depletion results in autoimmunity.6 A soluble form of the IL-2R alpha subunit (sIL-2Rα) is released into the serum from the membranes of activated lymphocytes after shedding by proteolytic cleavage.7 Release of sIL-2Rα is proportional to the cell surface expression of IL-2R.8 sIL-2Rα is detected in the serum of healthy individuals and increases in association with various types of inflammation or neoplasms. 5,9-11

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome of excessive immune system activation driven mainly by high levels of interferon gamma.2 HLH is induced by aberrantly activated macrophages and cytotoxic T cells.12 The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults.12 Guidelines for the diagnosis and prognostication of HLH include the measurement sIL-2Rα.13-17 Since T-cell activation is central to HLH pathogenesis, elevated sIL-2Rα is almost always observed in untreated HLH.18-20 Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory or autoimmune disorders, in which case it is called macrophage activation syndrome.12,21 Patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome.12 It has been suggested that sIL-2Rα can be a useful marker for the prognosis of patients with HLH that might help to stratify therapeutic interventions.22

Since T-cell activation is a hallmark of granuloma formation, diseases with extensive granulomatous lesions often present with elevated sIL-2Rα levels. sIL-2Rα has been reported to be an effective marker for measuring disease in patients with tuberculosis, sarcoidosis eosinophilic granulomatosis with polyangiitis and common variable immunodeficiency.4,23-28 Elevated levels have been reported in T-cell mediated diseases including multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis.29-33 Increased sIL-2Rα have also been reported in classical autoantibody mediated diseases including myasthenia gravis and pemphigus.34,35

Serum sIL-2Rα levels have been found to be elevated in most types of hematolymphoid neoplasms, including Hodgkin's lymphomas, non‑Hodgkin lymphomas, acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, and others.1 The highest levels of sIL-2Rα have been reported in adult T‑cell lymphoma/leukemia36 and hairy cell leukemia.37 Elevated levels have been reported in follicular and diffuse large B-cell lymphoma.5,38-43 An extremely elevated sIL-2Rα (>10- to 20-fold above normal) in a non-infantile patient suggests undiagnosed lymphoma, especially when ferritin is not similarly elevated.44,45 An association between increased levels of sIL-2Rα and poor outcome has also been reported in several non-lymphoid cancers.1,33,46


1. Bien E, Balcerska A. Serum soluble interleukin 2 receptor alpha in human cancer of adults and children: a review. Biomarkers. 2008 Feb;13(1):1-26.17906988
2. Gloude NJ, Dandoy CE, Davies SM, et al. Thinking Beyond HLH: Clinical Features of Patients with Concurrent Presentation of Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy. J Clin Immunol. 2020 Jul;40(5):699-707.32447592
3. Bode SF, Ammann S, Al-Herz W, et al. The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis. Haematologica. 2015 Jul;100(7):978-988.26022711
4. Schimmelpennink MC, Quanjel M, Vorselaars A, et al. Value of serum soluble interleukin-2 receptor as a diagnostic and predictive biomarker in sarcoidosis. Expert Rev Respir Med. 2020 Jul;14(7):749-756.32248706
5. Murakami J, Arita K, Wada A, et al. Serum soluble interleukin-2 receptor levels for screening for malignant lymphomas and differential diagnosis from other conditions. Mol Clin Oncol. 2019 Nov;11(5):474-482.31620278
6. Abbas AK. The Surprising Story of IL-2: From Experimental Models to Clinical Application. Am J Pathol. 2020 Sep;190(9):1776-1781.32828360
7. Rubin LA, Galli F, Greene WC, Nelson DL, Jay G. The molecular basis for the generation of the human soluble interleukin 2 receptor. Cytokine. 1990 Sep;2(5):330-336.2103332
8. Junghans RP, Waldmann TA. Metabolism of Tac (IL2Ralpha): physiology of cell surface shedding and renal catabolism, and suppression of catabolism by antibody binding. J Exp Med. 1996 Apr 1;183(4):1587-1602.8666917
9. Flynn MJ, Hartley JA. The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer. Br J Haematol. 2017 Oct;179(1):20-35.28556984
10. Damoiseaux J. The IL-2 - IL-2 receptor pathway in health and disease: The role of the soluble IL-2 receptor. Clin Immunol. 2020 Sep;218:108515.32619646
11. Kameda T, Shide K, Tahira Y, et al. Prognosis of Indolent Adult T-Cell Leukemia/Lymphoma. Viruses. 2022 Mar 29;14(4):710.35458440
12. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019 Jun 6;133(23):2465-2477.30992265
13. Janka GE, Schneider EM. Modern management of children with haemophagocytic lymphohistiocytosis. Br J Haematol. 2004 Jan;124(1):4-14.14675403
14. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-131.16937360
15. Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011 Oct 13;118(15):4041-4052.21828139
16. Hayden A, Park S, Giustini D, Lee AY, Chen LY. Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: A systematic scoping review. Blood Rev. 2016 Nov;30(6):411-420.27238576
17. Risma KA, Marsh RA. Hemophagocytic Lymphohistiocytosis: Clinical Presentations and Diagnosis. J Allergy Clin Immunol Pract. 2019 Mar;7(3):824-832.30557712
18. Lin M, Park S, Hayden A, et al. Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review. Ann Hematol. 2017 Aug;96(8):1241-1251.28497365
19. Hayden A, Lin M, Park S, et al. Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH. Blood Adv. 2017 Dec 6;1(26):2529-2534.29296904
20. Ladisch S, Nichols KE, Rodriguez-Galindo C, et al. Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO). Pediatr Blood Cancer. 2019 Nov;66(11):e27929.31339233
21. Fattizzo B, Ferraresi M, Giannotta JA, Barcellini W. Secondary Hemophagocytic Lymphohistiocytosis and Autoimmune Cytopenias: Case Description and Review of the Literature. J Clin Med. 2021 Feb 20;10(4):870.33672504
22. Wimmer T, Mattes R, Stemmler HJ, et al. sCD25 as an independent adverse prognostic factor in adult HLH patients: results of a multicenter retrospective study. Blood Adv. 2022 Aug 16;bloodadvances.2022007953.35973195
23. Vanmaris RMM, Rijkers GT. Biological role of the soluble interleukin-2 receptor in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2017;34(2):122-129.32476833
24. Takahashi S, Setoguchi Y, Nukiwa T, Kira S. Soluble interleukin-2 receptor in sera of patients with pulmonary tuberculosis. Chest. 1991 Feb;99(2):310-314.1989787
25. Chan CH, Lai CK, Leung JC, Ho AS, Lai KN. Elevated interleukin-2 receptor level in patients with active pulmonary tuberculosis and the changes following anti-tuberculosis chemotherapy. Eur Respir J. 1995 Jan;8(1):70-73.7744196
26. Grutters JC, Fellrath JM, Mulder L, Janssen R, van den Bosch JMM, van Velzen-Blad H. Serum soluble interleukin-2 receptor measurement in patients with sarcoidosis: a clinical evaluation. Chest. 2003 Jul;124(1):186-195.12853522
27. Eurelings LEM, Miedema JR, Dalm VASH, et al. Sensitivity and specificity of serum soluble interleukin-2 receptor for diagnosing sarcoidosis in a population of patients suspected of sarcoidosis. PLoS One. 2019 Oct 17;14(10):e0223897.31622413
28. Stegeman CA, Tervaert JW, Huitema MG, Kallenberg CG. Serum markers of T cell activation in relapses of Wegener's granulomatosis. Clin Exp Immunol. 1993 Mar;91(3):415-420.8443965
29. Maier LM, Anderson DE, Severson CA, et al. Soluble IL-2RA levels in multiple sclerosis subjects and the effect of soluble IL-2RA on immune responses. J Immunol. 2009 Feb 1;182(3):1541-1547.19155502
30. Giordano C, Galluzzo A, Marco A, et al. Increased soluble interleukin-2 receptor levels in the sera of type 1 diabetic patients. Diabetes Res. 1988 Jul;8(3):135-138.3265901
31. Greenberg SJ, Marcon L, Hurwitz BJ, Waldmann TA, Nelson DL. Elevated levels of soluble interleukin-2 receptors in multiple sclerosis. N Engl J Med. 1988 Oct 13;319(15):1019-1020.3138540
32. Semenzato G, Bambara LM, Biasi D, et al. Increased serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and rheumatoid arthritis. J Clin Immunol. 1988 Nov;8(6):447-452.3065351
33. Witkowska AM. On the role of sIL-2R measurements in rheumatoid arthritis and cancers. Mediators Inflamm. 2005 Aug 14;2005(3):121-130.16106097
34. Confalonieri P, Antozzi C, Cornelio F, Simoncini O, Mantegazza R. Immune activation in myasthenia gravis: soluble interleukin-2 receptor, interferon-gamma and tumor necrosis factor-alpha levels in patients' serum. J Neuroimmunol. 1993 Oct;48(1):33-36.8227305
35. Zillikens D, Ambach A, Zentner A, et al. Evidence for cell-mediated immune mechanisms in the pathology of pemphigus. Br J Dermatol. 1993 Jun;128(6):636-643.8338748
36. Yasuda N, Lai PK, Ip SH, et al. Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease. Blood. 1988 Apr;71(4):1021-1026.2895675
37. Ambrosetti A, Nadali G, Vinante F, et al. Soluble interleukin‑2 receptor in hairy‑cell leukemia: A reliable marker of disease. Int J Clin Lab Res. 1993;23(1):34-37.8477089
38. Niitsu N, Iijima K, Chizuka A. A high serum-soluble interleukin-2 receptor level is associated with a poor outcome of aggressive non-Hodgkin's lymphoma. Eur J Haematol. 2001 Jan;66(1):24-30.11168504
39. Yang ZZ, Grote DM, Ziesmer SC, et al. Soluble IL-2Rα facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma. Blood. 2011 Sep 8;118(10):2809-2820.21719603
40. Morito T, Fujihara M, Asaoku H, et al. Serum soluble interleukin-2 receptor level and immunophenotype are prognostic factors for patients with diffuse large B-cell lymphoma. Cancer Sci. 2009 Jul;100(7):1255-1260.19432905
41. Jo SA, Hwang SH, Chang CL, et al. Clinical relevance of elevated levels of serum soluble interleukin-2 receptor alpha (sIL-2Rα) in patients with non-Hodgkin's lymphoma. Korean J Lab Med. 2010 Dec;30(6):600-605.21157146
42. Yoshizato T, Nannya Y, Imai Y, Ichikawa M, Kurokawa M. Clinical significance of serum-soluble interleukin-2 receptor in patients with follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2013 Aug;13(4):410-416.23747081
43. Yoshida N, Oda M, Kuroda Y, et al. Clinical significance of sIL-2R levels in B-cell lymphomas. PLoS One. 2013 Nov 13;8(11):e78730.24236041
44. Gurunathan A, Boucher AA, Mark M, et al. Limitations of HLH-2004 criteria in distinguishing malignancy-associated hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2018 Dec;65(12): e27400.30272386
45. Tsuji T, Hirano T, Yamasaki H, Tsuji M, Tsuda H. A high sIL-2R/ferritin ratio is a useful marker for the diagnosis of lymphoma-associated hemophagocytic syndrome. Ann Hematol. 2014 May;93(5):821-826.24705932
46. Murakami S. Soluble interleukin-2 receptor in cancer. Front Biosci. 2004 Sep 1;9:3085-3090.15353339


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
142455 IL-2 Receptor Alpha 44422-4 142457 IL-2 Receptor Alpha U/mL 44422-4

For Providers

Please login to order a test

Order a Test

© 2021 Laboratory Corporation of America® Holdings and Lexi-Comp Inc. All Rights Reserved.

CPT Statement/Profile Statement

The LOINC® codes are copyright © 1994-2021, Regenstrief Institute, Inc. and the Logical Observation Identifiers Names and Codes (LOINC) Committee. Permission is granted in perpetuity, without payment of license fees or royalties, to use, copy, or distribute the LOINC® codes for any commercial or non-commercial purpose, subject to the terms under the license agreement found at Additional information regarding LOINC® codes can be found at, including the LOINC Manual, which can be downloaded at