Interleukin-2 Soluble Receptor α

Serum, frozen

0.5 mL

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

Red-top tube or gel-barrier tube

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)

223−710 units/mL

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