Pretreatment Serum Soluble Interleukin-2 Receptor Levels Predict the Response after Immunosuppressive Therapy of Aplastic Anemia.

Severe aplastic anemia (SAA), characterized by pancytopenia and a hypocellular marrow, has heterogenous pathophysiologic mechanisms including a stem-cell defect or a T-cell disease. Immunosuppressive (IS) therapy based on antilymphocyte globulin (ALG) and cyclosporine (CsA) improved the response rate in patients with SAA not eligible for stem cell transplantation. The goal of IS regimens in SAA is elimination of T cells effecting the immune-mediated destruction of hematopoietic progenitor and stem cells. Increased levels of soluble interleukin-2 receptor (sIL2R) have been detected in patients with high immune activity such as autoimmune diseases, allograft rejection, and severe infection. Twenty-eight patients with SAA (15 males and 13 females, median age 27 years, range 16–62) were given an ALG (Lymphoglobuline, Institut Pasteur Merieux, 15mg/kg/day intravenously from day 1 to 5) and CsA (5mg/kg/day orally from day 12 to 180). We measured the serum sIL2R levels using ELISA test kit (CELLFREE IL-2R Medex, Kyowa, Japan) in 28 patients with SAA before and after therapy with ALG+CsA. The mean serum sIL2R levels at baseline, 7 and 60 days after ALG treatment were 572.8 pg/ml (range 181–1715), 2156.3 pg/ml (range 211–7315) and 488.0 pg/ml (range 168–1411), respectively. The baseline sIL2R levels were significantly higher in our patients when compared with normal control subjects (n=26, 379±164 pg/ml, P=0.01). Overall response, defined as transfusion independence, was achieved in 12/28 (42.9%) patients on 180 days after treatment. The baseline serum sIL2R levels were elevated more than the normal control mean+1SE (541 pg/ml) in 7 of 12 patients with response but in 4 of 16 without response (Pearson Chi-Square, P=0.047). According to the baseline sIL2R levels, the positive predictive value (the number of patients with response/>control mean+1SE) was 63.6% (7/11) and the negative predictive value (the number of patients who failed to obtain the response/<control mean+1SE) was 70.6% (12/17). The sIL2R levels on both day 7 and 60 did not show any difference between the groups. Overall, these findings demonstrate that serum sIL2R levels increase in patients with aplastic anemia. Pretreatment serum levels of sIL2R might be closely related to clinical outcome following IS therapy, reflecting the immunological abnormalities in individual patients.