Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity

Abstract

In this study we provide evidence that the sera of patients with hairy cell leukemia (HCL) contain a factor that can prevent the binding of a monoclonal antibody specific for interleukin-2 receptor (IL-2R) to its target. This factor corresponds to the soluble form of IL-2R (sIL-2R), as assessed by a specific enzyme-linked immunosorbent assay test, and appears to be released by neoplastic hairy cells. The serum sIL-2R levels were very high at diagnosis and significantly reduced during recombinant alpha-interferon (rIFN alpha 2) therapy. Values of sIL-2R appeared to be inversely related to the natural killer in vitro function displayed by peripheral blood mononuclear cells from the same patients. The presence of sIL-2R in the serum of patients with HCL might be involved in the impairment of cell-mediated immunity observed in these patients and could represent a valuable marker for monitoring different phases of the disease and for modulating IFN therapy.

Aggressive disease defined by cytogenetics is associated with cytokine dysregulation in CLL/SLL patients

“…Of particular interest was the presence and degree of amplification in sIL-2R␣ in HCs versus GR and HCs versus int/PR ( Table 3) in this study. High levels of sIL-2R␣ are known to have an immunomodulatory effect, reported to predict for an unfavorable prognosis in a variety of hematologic malignan- cies, including FL [25], cutaneous T cell lymphoma [26], hairy cell leukemia [27], and CLL [28]. The immunomodulatory role of sIL-2R␣ appears to be pleiotropic depending on the disease state.…”

Serum Level of Soluble Interleukin‐2 Receptor in Patients with Seasonal Allergic Rhinitis

“…The serum samples were separated and stored at ¹80ЊC, and were simultaneously used for determination of soluble IL-2R concentrations and Japanese cedar pollen-specific IgE antibodies. Two monoclonal antibodies (MoAb) recognizing different epitopes of the IL-2R molecules were used in an enzyme-linked immunosorbent assay (ELISA) (Cellfree, T Cell Science, Cambridge, MA, USA), as previously described by Chilosi et al [13]. In brief, soluble IL-2R available in the samples or standard bind to the polystyrene microtitre was previously incubated with 100 mL anti-IL-2R MoAb (1mg/mL).…”

Rapid restoration of natural killer activity following treatment with 2‐chlorodeoxyadenosine in 22 patients with hairy‐cell leukemia

“…Several immunological abnormalities have been reported in patients with HCL (3-9) including an impairment of the NK compartment which may be altered with different mechanisms, encompassing factors from a reduced number of NK effector cells to a decreased functional ability of these cells to bind and kill target cells (7-9). In addition, it has been hypothesized that the NK function in these patients might also be blocked by the excessive amounts of sIL-2R produced by the HC themselves (29).…”

“…This observation does suggest that the reduced cytotoxic capacity in our patients was probably due to a reduced proportion of NK-cells. Additional mechanisms, such as the blocking effect of the increased serum level of sIL-2R on the NK activity, have been reported in the past on the basis of a correction between improvement of NK activity and decrease of sIL-2R serum level following g-lFN therapy (7,29). Even in our study the rapid normalization of sIL-2R serum levels parallelled the normalization of the NK activity, and viceversa; however, it should be pointed out that the "blocking" role of sIL-2R is not supported by any laboratoristic demonstration (3 1).…”