In vitro effects of IL-2 on NK-activity, clonogenic potential, blast cell proliferation and cytokine release of MDS bone marrow patients.

To evaluate the clinical usefulness of IL-2 in myelodysplastic syndromes (MDS) the in vitro effects of interleukin-2 (IL-2) on blast cell proliferation, clonogenic activity, cytokine release and cell mediated cytotoxicity were examined in 49 MDS patients. Morphological analyses of bone marrow (BM) cytospin preparations showed a significant decrease in the number of blast cells in MDS after incubation with IL-2. Incubation of bone marrow mononuclear cells (BMMNCs) with IL-2 induced a significant increase in the number of CFU-GM in comparison with untreated controls. gamma-IFN and GM-CSF, but not alpha-TNF were found to be released in significant amounts by the BMMNCs cultured with IL-2. No significant differences in the surface phenotypes of fresh lymphocytes were observed between the normal and MDS subjects. After incubation with IL-2, we observed a significant increase in the number of CD3-/CD56+ cells in both normal and MDS subjects. Peripheral blood (PB) and BM NK activity against K562 was significantly greater in MDS after stimulation with IL-2. These data suggest the clinical usefulness of IL-2 in a large subgroup of patients as it may reduce the percentage of blasts and increase clonogenic capacity and cell-mediated cytotoxicity.

Takayasu's arteritis in Italian patients.

OBJECTIVE: To evaluate the clinical features, angiographic findings and evolution of Takayasu's arteritis in Italian patients. METHODS: Retrospective analysis of the case records of 27 Italian patients with Takayasu's arteritis, all meeting the 1990 ACR criteria for classification of this vasculitis, with a median disease duration of 9.5 years. RESULTS: The patterns of arterial involvement and the frequencies of systemic and specific symptoms were similar, with some exceptions, to those reported in the literature. In our patients weight loss was rare, the incidence of respiratory symptoms and seizures was low, and no clinical manifestations of intestinal involvement were reported. All of the patients were treated with antiplatelet or anticoagulant medications, and 14 were also treated with corticosteroids and immunosuppressants; a stabilization of the vascular involvement was seen in most of them. Thirteen patients underwent surgery, and 5 had percutaneous transluminal renal angioplasties. Five pregnancies were observed, without complications. Two patients died, one after an angiographic evaluation and one for reasons unrelated to the disease. CONCLUSIONS: Takayasu's arteritis is heterogeneous in presentation, evolution and response to therapy. In our series of patients the disease seems to have showed a more favorable course than that previously reported. This can be attributed to the effectiveness of therapy, but also, at least partially, to the better prognosis that the disease seems to have for Western than for Eastern subjects.

Relationship between antibodies to dsDNA and to soluble cellular antigens and histologically defined glomerulonephritis in patients with SLE.

To better define the relationships between circulating autoantibodies and renal involvement in systemic lupus erythematosus (SLE), antibodies to both dsDNA and soluble cellular antigens were detected in sera from a large series of SLE patients. Significantly higher dsDNA binding activities and lower complement levels at onset were found in patients with renal disease; however, this was uniquely due to subjects with diffuse or focal proliferative glomerulonephritis. Patients with membranous nephropathy (MGN) showed very low dsDNA binding activities (6/9 of them being negative for dsDNA antibodies) and normal mean C3 and C4 levels. A comparison between patients with proliferative nephritis and patients without renal involvement with high dsDNA binding activities revealed significantly lower complement levels in the former group. No significant difference was observed in the prevalence of antibodies to soluble cellular antigens between patients with or without renal disease; however, nRNP antibody was two-fold more frequent in patients with MGN than in all other subgroups. This study highlights the close relationship between concurrently high anti-dsDNA and low complement levels and proliferative glomerulonephritis in SLE, and suggests that subjects with MGN may represent a subgroup of SLE patients showing peculiar serological features. Different mechanisms possibly involved in the pathogenesis of MGN in SLE are discussed.

In vivo enhancement of NK-cell activity by thymopentin.

Natural killer (NK) activities of fresh and IL-2-precultured peripheral blood mononuclear cells (PBMC) were investigated in 13 elderly subjects before and after thymopentin (TP-5) treatment and in 12 age-matched controls. The NK activity of fresh PBMC was found to be significantly higher in subjects given TP-5 at 50 mg s.c. three times per week for one month. Conversely, this type of treatment with TP-5 did not significantly modify the cytotoxic capacity of IL-2-precultured PBMC.

NK cells in patients with peripheral neuropathy and IgM monoclonal protein reacting with the myelin-associated glycoprotein (MAG).

We studied Leu 7+ cell distribution and natural killer (NK) activity in the peripheral blood of six patients who had peripheral neuropathy and monoclonal IgM protein directed against myelin-associated glycoprotein (anti-MAG IgM). We did not find any difference between patients and control subjects (healthy or polyneuropathic, some with IgM monoclonal paraprotein but without anti-MAG activity). The presence of autologous sera did not interfere with these results. We noted an increase in Leu 11+ cell percentages after pre-incubation of the patient cells with autologous sera but the phenotypes of cells from control subjects did not change after incubation with autologous or patient sera.

Antibodies to Epstein-Barr virus and cytomegalovirus in primary Sjogren's syndrome.

Sera from 28 patients with Primary Sjögren's Syndrome (SS) and 20 healthy subjects were tested for the presence of antibodies to Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV). No difference was noted in the mean titre of anti-CMV antibodies in patients and in controls. For what concerns EBV, the mean titre of anti-EBNA antibodies was significantly higher in SS patients than in normals (p less than 0.001); moreover, within the SS population, titres were higher in SSB-positive than in SSB-negative patients (p less than 0.05). These results, together with the fact that anti-SSB antibodies (characteristic of Sjögren's Syndrome) recognize also two EBV-encoded RNAs, strengthen the hypothesis that EBV is involved in the pathogenesis of SS.

Age- and sex-dependent changes in natural killer cell activity.

Peripheral blood mononuclear cells (PBMC) from 40 normal individuals, 20 men and 20 women, divided according to age were evaluated for their ability to mediate natural killer (NK) cytotoxicity, using the K562 erythroleukemic cells as target. The results of a specific 51Cr release assay demonstrated that NK activity was greater in men than in women. There was a significant correlation between NK activity and the percentages of Leu 11a+ cells in younger women, but not in the other groups and no correlation between NK activity and Leu 7+ cells.