Soluble interleukin-2 receptor levels in patients with undifferentiated and lymphoblastic lymphomas: correlation with survival.

Abstract

We have been able to detect soluble interleukin-2 receptors (IL-2R) in pretreatment sera from 80 patients with undifferentiated lymphoma (predominantly Burkitt's lymphoma) and lymphoblastic lymphoma. The demonstration of IL-2R in lymphoma-derived cell lines by immunoprecipitation and direct staining indicates that IL-2R is synthesized by the tumor cells. Comparisons were made with two other subject groups: 42 sarcoma patients and 17 normal individuals. The distribution of soluble IL-2R values for lymphoma patients (geometric mean, 1,132 U/mL) was significantly greater than that of sarcoma patients (geometric mean, 332 U/mL; P = .0001) or normal individuals (geometric mean, 238 U/mL; P = .0001). Patients with undifferentiated lymphoma stages B, C, and D had significantly higher soluble IL-2R values (geometric mean, 1,648 U/mL) than stages A and AR (geometric mean, 706 U/mL; P = .0001) or lymphoblastic lymphoma (geometric mean, 826 U/mL; P = .0002). Within the lymphoma group, the soluble IL-2R level was found to be the most significant prognostic indicator of disease-free interval and survival when compared with other previously recognized factors such as histology, stage, bone marrow involvement at presentation, lactic dehydrogenase (LDH), uric acid (UA), and age. No factor was significantly associated with response to therapy, ie, the initial achievement of complete remission (CR) status, although small numbers of patients with a partial response limit interpretation. Soluble IL-2R levels were measured serially in two patients and were found to be elevated at presentation or relapse and to decrease to normal levels during periods of disease remission. IL-2R appears to reflect tumor burden and may prove to be a useful and specific marker for lymphoid tumors.

Elevated soluble interleukin‐2 receptor levels in the sera and synovial fluids of patients with rheumatoid arthritis

“…Campen et a1 (25) have recently reported that serial measurements of serum IL-2R in a group of patients with active systemic lupus erythematosus demonstrated a decline from initial markedly elevated levels toward normal levels with clinical improvement. In addition, the level of serum IL-2R at the time of initial diagnosis has proven (e.g., in undifferentiated and lymphoblastic lymphoma) to be the most accurate predictor of disease-free survival at 5 years (26). The level in these patients was thought to be a very sensitive reflection of tumor burden, more so than currently used parameters.…”

Raised serum levels of CD8, CD25 andβ2-microglobulin in common variable immunodeficiency

“…For example, it has been reported that culture supernatants of synovial fluid mononuclear cells from patients with rheumatoid arthritis contain levels of sol-CD8 and sol-CD25 in an inverse relationship (Symons et al, 1990), What causes the raised serum levels of sol-CD8, /ii-M and sol-CD25? High levels of these soluble molecules have been associated with viral infections, in particular of HIV and HTLV-1 (Bhalla et cd., 1983;Rubin, Jay & Nelson, 1986;Yasuda et al, 1988;Reddy et cd., 1989), Interestingly, in HIV infection serum levels of sol-CD4 are also elevated (Reddy et al, 1990) but we have now shown that this does not occur in CVI, In infectious mononucleosis the levels of sol-CD8 are raised and correlate with the numbers of activated CD8+/HLA DR+ cells (Tomkinson et cd., 1989), However, patients with CVI are not unduly susceptible to common viral infections (Asherson & Webster, 1980), In addition, attempts to link CVI with a chronic viral infection have so far failed (Spickett et cd., 1988;Webster & Sa'adu, 1991), Lymphoproliferative disorders have been associated with elevations in soluble lymphocyte receptors in sera (Fujimoto et al, 1983;Wagner et al, 1987;Pui et cd., 1988;Steis et al, 1988;Ho et at., 1990), However, none of the CVI patients in the present study had malignant lymphoid disease, Lymphoeyte activation in vitro, for example with PHA, releases sol-IL-2R and sol-CD8 (Nelson et al, 1986;Hsieh, 1989), In synovial mononuclear cells from patients with rheumatoid arthritis there is evidence that activation with TNF-a can induce the release of S0I-CD8 (Symons e/fl/,, 1990), For this reason we measured the serum levels of TNF-a in CVI, However, TNF-a does not seem to be involved in CVI since the raised levels of S0I-CD8 were not accompanied by any changes in serum TNF-a, What is the functional significance ofthe raised levels of sol-CD8, ^2-M and sol-CD25 in CVI? It is known that membrane CD8 binds to HLA class I on other cells (Solheim, 1974), Although the functional significance of S0I-CD8 is not clear, it is possible that it could inhibit immune function by competing with membrane bound CD8 (on T cytotoxic or suppressor cells) in its interaction with HLA class I, This could lead to complex effects.…”

Serum levels of soluble interleukin-2 receptors and their relation to lymphocyte subpopulations in patients with metastatic solid tumours

“…High serum levels of soluble interleukin-2 receptors (sIL-2R) have been observed in patients suffering from malignant lymphomas, either in Hodgkin's disease (Pizzolo et al, 1987) or in non-Hodgkin's lymphomas (Wagner et al, 1987), and in those affected by leukaemia (Chilosi et al, 1986). Moreover, recent studies have shown that elevated concentrations of sIL-2R can also be found in patients with disseminated solid tumours (Rovelli et al, 1988).…”