C. Vincenzi

ICAM‐1 tissue overexpression associated with increased serum levels of its soluble form in Hodgkin's disease

Summary. We investigated ICAM‐1/CD54 tissue immunoreactivity and serum levels of its soluble form (sICAM‐1) in patients with Hodgkins disease (HD) at diagnosis. ICAM‐1 was strongly expressed in involved tissues, and sICAM‐1 serum levels were higher in HD (79 patients) than in controls (P < 0 · 01), and in patients with more advanced or more active disease (stages III ± IV vI ± II: P= 0 · 002; stage ‘B’v‘A’: P <0 · 0001; ‘bulky’disease v non‐‘bulky’: P= 0 · 042). We suggest that tissue ICAM‐1 overexpression leading to increase of circulating sICAM‐1 may interfere with the lymphocyte adhesion machinary thus contributing to the well‐known immune derangement of HD.

Serum levels of soluble interleukin‐2 receptor in hairy cell leukaemia: a reliable marker of neoplastic bulk

In hairy cell leukaemia (HCL), the strong membrane expression of the Tac antigen, corresponding to the p55 chain of the interleukin‐2 receptor (IL‐2R), is associated with the presence in the serum of high levels of a soluble form of the same molecule (sIL‐2R). Previous observations that therapy‐induced clinical and haematologic improvement in HCL is accompanied by a progressive decrease of sIL‐2R suggest a possible correlation between sIL‐2R levels and tumour burden. To verify this hypothesis, we monitored the variation of sIL‐2R values in 13 non‐splenectomized HCL patients admitted for treatment with recombinant interferon alpha‐2. The data were correlated with the estimated weight of bone marrow (BM) and spleen infiltrations, which in these patients almost entirely account for the tumour mass. The regression analysis test showed a direct correlation between sIL‐2R values and both BM neoplastic involvement (r= 0.63) and spleen tumour mass (r= 0.76). In addition, the correlation was further improved (r= 0.86) when sIL‐2R values were correlated with the total neoplastic mass, as calculated by the sum of spleen and BM neoplastic tissue weight. These data indicate that the detection of sIL‐2R in HCL is a reliable non‐invasive marker of tumour burden, which can be regarded as an additional useful tool for monitoring treatment response.

Highly concentrated urine-purified Tac peptide fails to inhibit IL-2-dependent cell proliferation in vitro

Tac peptide, i.e., the p55 chain of the human interleukin-2 receptor (IL-2R) complex, is detectable as a soluble from (sIL-2R) in normal sera and, at increased levels, in patients with different diseases. Since several immunological abnormalities are observed in most conditions associated with an increase in sIL-2R levels, a down-regulatory effect on IL-2-dependent functions has been postulated as a consequence of binding and functional block of IL-2 by the excess of sIL-2R. To test this hypothesis, we purified sIL-2R from the urine of a patient with hairy cell leukemia and investigated the possible inhibitory effect of this peptide on the in vitro IL-2-induced cell proliferation. The urine-purified molecule was detectable by the specific immunoassay utilized to measure the serum Tac peptide and was constructed by a single polypeptide of about 50 kDa which was able to bind IL-2. Experiments performed with the IL-2-dependent murine CTLL-2 cell line and with PHA-stimulated human peripheral blood mononuclear cells showed that the purified sIL-2R at concentrations up to about 300 nM was unable to block IL-2-dependent cell proliferation. According to these data, which can be explained by the low affinity for IL-2 of the p55 IL-2R chain, it seems unlikely that in vivo the soluble Tac peptide can exert a down regulatory effect on IL-2-induced phenomena through a functional block of IL-2.

Circulating levels of soluble CD23 reflect clinical and biological features of leukemic B-cell chronic lymphoproliferative disorders

SummaryOne hundred and twenty-four sera, from patients with various leukemic B-cell chronic lymphoproliferative diseases were investigated at diagnosis by ELISA for their soluble CD23 content. Immunophenotyping was carried out in all patients, and in a selected subset the mean number of membrane-bound CD23 molecules per cell was also investigated. Seventy-three patients had typical B chronic lymphocytic leukenia, 41 leukemic B-cell disorders with atypical morphological and/or immunophenotypic features, 5 had low-grade follicular cell lymphoma in the leukemic phase, and 5 had splenic lymphoma with villous lymphocytes Soluble CD23 levels were significantly higher than in normal sera (mean±SD: typical B chronic lymphocytic leukemia 3,650±4,654 U/ml, atypical B chronic lymphocytic leukemia 3,440±4,671 U/ml, follicular cell lymphoma 3,200±1,511 U/ml, splenic lymphoma with villous lymphocytes 8,236±7,294 U/ml, controls 137±128 U/ml;P<0.001). More advanced Rais stages were related to higher soluble CD23 levels (P<0.01), both in typical and atypical B chronic lymphocytic leukemias, the highest levels and the best correlation with the absolute number of circulating CD19+ cells (r=0.50) being observed in the typical form. The number of membrane-bound CD23 molecules per cell was significantly higher in typical than in atypical B chronic lymphocytic leukemias (mean number 156,727±94,668 vs. 12,010±10,643,P<0.001). Our data suggest that soluble CD23 levels correlate with the clinical and biological features of leukemic B-cell lymphoproliferative disorders.