Soluble interleukin-2 receptor in Sezary syndrome: its origin and clinical application

Abstract

Soluble interleukin-2 receptor (sIL-2R) serum levels were evaluated in Sézary syndrome (SS), mycosis fungoides, non-epidermotropic T-cell lymphomas, inflammatory skin diseases (eczema, psoriasis and lichen planus) and benign erythroderma. All groups displayed mean values significantly higher than controls, and values in SS were also significantly higher than those in the other diseases investigated. Follow-up of 17 SS patients showed that serum sIL-2R correlated with the clinical course of the disease and with other haematological parameters (absolute number of circulating Sézary cells, lactic dehydrogenase). Culture experiments demonstrated that, in contrast with other haematological disorders, highly enriched resting Sézary cells were unable to release sIL-2R, and failed to release normal amounts even after mitogen stimulation. Nevertheless, the leukaemic burden, together with the activation and consequent CD25 expression of leukaemic lymphocytes infiltrating the skin, may justify the hypothesis of a neoplastic sIL-2R source. To further support this hypothesis, the highest sIL-2R values were found in patients with advanced disease, in which normal reactive lymphocytes were dramatically reduced.

The expression of MUM1 in cutaneous T-cell lymphoproliferative disorders

“…It was shown previously that MUM1 is important for IL-2 production and response [4]. In fact, the serum level of CD25 (IL-2R), an interleukin receptor expressed on activated T cells, was reported to be increased in SS and advanced MF [24]. Increased CD25 in skin specimens was identified in a subset of LCT and correlated with CD30 positivity [20,25].…”

Soluble receptors in human disease

“…In ATLL, the malignant cells have high expression of membrane-bound IL-2 receptors, so that the concentration of soluble IL-2 receptor in the serum is probably an indirect measure of tumor burden. Soluble IL-2 receptors are similarly elevated in patients with Sezary's syndrome and hairy cell leukemia which, as malignancies of activated lymphocytes, often have substantial surface expression of IL-2 receptors [153,154]. Irrespective of whether soluble IL-2 receptor expression is increased in response to a nonspecific stimulus such as inflammation or results directly from release from proliferating tumor cells, it is important to consider that soluble IL-2 receptor is likely to have intrinsic biological activity and may act as an immunosuppressant (see above).…”

Serum Soluble Interleukin 2 Receptor Levels in Erythrodermic Cutaneous T-Cell Lymphoma Correlate With Response to Photopheresis-Based Treatment

“…The SIL2R-modified alpha-chain homodimer6 structure is distinct from those of the cell surface high-or intermediate-affinity IL2R heterodimers.4'5 However, SIL2R does maintain low affinity interleukin-2 binding capacity.26 In the context of T-cell clonal expansion, SIL2R may be produced mainly by ma¬ lignant cells. 2,12,27 Because of the paucity of simple, standardized indi¬ cators of patient improvement or progression in CTCL, an objective, efficient, and easily reproducible marker would be a valuable addition to the future care of these patients.…”