No abstract

SUMMARYThere is evidence that both cellular and humoral components of the immune response are required for viral clearance to occur in chronic hepatitis B. Recent studies demonstrated that CD30 molecule, a member of the tumour necrosis factor superfamily of membrane cytokine receptors, is expressed on, and released as a soluble molecule (sCD30) by activated T cells producing T helper 2 (Th2) cytokines, which modulate antibody responses. To better characterize the immunoregulatory mechanisms in chronic hepatitis B virus (HBV) infection, sCD30 values were evaluated by an ELISA in 90 hepatitis B surface (HBsAg)-positive patients with chronic hepatitis, selected on the basis of active viral replication and biochemical activity. At presentation abnormal levels (>20 U/ml) of sCD30 were detected in 57 (63%) out of 90 patients with chronic hepatitis B, and median value was significantly higher in this group of patients compared with that of healthy HBsAg carriers (26 . 7 versus 10 . 5 U/ml, P < 0 . 000 05) and with normal controls (26 . 7 versus 3 U/ml, P < 0 . 000 01). Sequential studies of chronic hepatitis B did confirm the association of raised sCD30 levels with the active phase of the illness. On the other hand, a significant decrease was noted when sCD30 levels at diagnosis and after termination of HBV replication and biochemical remission of hepatitis were compared in 10 untreated patients (median, 28 U/ml at entry versus 8 U/ml at remission, P < 0 . 01) and in six patients responding to interferon-alpha therapy (median, 29 . 5 U/ml at entry versus 6 U/ml at remission, P < 0 . 05). The high serum sCD30 levels reported during the active phase of HBsAg-positive chronic hepatitis suggest a certain degree of immune competence of these patients, at least with respect to a Th2-type response. These data are in agreement with recent serologic surveys showing that most chronic hepatitis B patients do demonstrate ongoing humoral immune response to HBV antigens, using novel immunoassays designed to detect antibody in the presence of excess serum viral antigen. Th2 functions that mainly promote humoral immunity to HBV antigens may be critical, in association with a competent virus-specific cytotoxicity, for efficient termination of HBV replication in chronic hepatitis B.

SUMMARYIn order to investigate the T cell cytokine profile during age-dependent maturation of the immune response, we evaluated the cytokine expression of CD4 þ and CD8 þ circulating cells by flow cytometric single-cell analysis after non-specific stimulation in vitro in different age groups of normal individuals, from cord blood to adulthood. Moreover, we correlated these lymphocyte cytokine patterns with the expression/release of CD30, a member of the tumour necrosis factor (TNF) receptor superfamily, which has been suggested to be related to the T helper/cytotoxic (Th(c))2-type immune responses, in order to verify this association in vivo, in non-pathological conditions. The results showed a progressive increase of circulating Th(c)1-type, interferon-gamma (IFN-g)-and/or IL-2-producing T cells along with ageing and, conversely, a stable number, although higher than in cord blood samples, of CD4 þ /IL-4 þ T cells in the post-natal groups. In addition, serum levels of soluble CD30 (sCD30) and numbers of circulating CD4 þ /CD30 þ and CD8 þ /CD30 þ T cells were significantly higher in children aged < 5 years in comparison with those found either in cord blood or in blood from both older children and adults. These data support the concept of a progressive polarization of the Th(c) cell cytokine profile towards the Th(c)1 pattern during age-dependent maturation of the immune response. Moreover, the peak of CD30 expression/release in early infancy before the Th(c)1 shifting occurs, although not associated with a significant increase of circulating IL-4 þ T cells, raises the question of the possible relationship in vivo between CD30 and Th(c)2-type immune responses.

sCD30 appears to be a new biologic serum tumor marker of possible use in the clinical setting of CD30+ ALCL.

SUMMARYCD30 has been suggested to play a role in HIV infection. In this study the serum concentration of soluble CD30 (sCD30) was determined by an ELISA essay on samples collected from patients with acute primary HIV-1 infection during the acute phase (n ¼ 17) and after seroconversion (n ¼ 13). sCD30 during acute infection was consistently elevated (137·58 Ϯ 120·33 versus 6·4 Ϯ 5·4 U/ml (mean Ϯ s.d.) in normal controls; P < 0 . 0001) and decreased after seroconversion (49·1 Ϯ 66·17 U/ml; P ¼ 0 . 0018 compared with acute infection). This trend mirrored the disappearance of detectable levels of HIV antigen in the blood, resulting in a direct correlation between sCD30 and HIVAg values (P ¼ 0 . 002). These data suggest that the high levels of sCD30 observed during the peak concentration of HIVAg in acute primary HIV infection might reflect the high rate of viral replication.

Summary. The tumour necrosis factor (TNF)/TNF-receptor (TNFR) complex plays a role in the growth of leukaemic cells. We retrospectively investigated the relationship between pretreatment serum concentration of soluble TNFR (p55-and p75-sTNFRs) and outcome in adult acute myeloid (AML 82 cases) and lymphoid (ALL 44 cases) leukaemia. Both sTNFRs were significantly higher in AML (p55-sTNFR 4 . 53 Ϯ 3 . 7, median 3 . 75; p75-sTNFR 6 . 51 Ϯ 5 . 25 ng/ml, median 4 . 72) and ALL sera (3 . 31 Ϯ 1 . 5, median 2 . 95; 5 . 30 Ϯ 2 . 3 ng/ml, median 4 . 56, respectively) than in controls (1 . 89 Ϯ 0 . 5, median 1 . 98; 2 . 22 Ϯ 0 . 8 ng/ml, median 2 . 37) (P < 0 . 01 for both sTNFRs). Fresh leukaemic cells expressed p55-and p75-sTNFRs, which were modulated and released into the supernatant (SN) following short-term in vitro culture, suggesting that in vivo sTNFRs were also leukaemia-derived. Whereas no correlation was observed between sTNFRs and outcome in ALL, in AML higher p55-sTNFR levels (> 3 . 75 ng/ml) were associated with shorter disease-free survival (DFS) (P ¼ 0 . 006) and overall survival (OS) (P ¼ 0 . 0004). At multivariate analysis p55-sTNFR was the most significant predictor of DFS (P ¼ 0 . 006) and OS (P < 0 . 001). Our data suggest that the prognostic significance of p55-sTNFR in AML could be related to relevant biological features of AML blasts.

We investigated ICAM-1/CD54 tissue immunoreactivity and serum levels of its soluble form (sICAM-1) in patients with Hodgkin's 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 machinery thus contributing to the well-known immune derangement of HD.

The CD25 molecule, which corresponds to the p55 alpha chain of the interleukin-2 receptor, is strongly expressed by neoplastic cells in hairy-cell leukemia and is released in large amounts in the soluble form which is detectable in serum. In order to assess the reliability of the soluble interleukin-2 receptor as a disease marker in the management of patients with hairy-cell leukemia, we investigated serum levels in 35 untreated patients and in 2 patients with the hairy-cell leukemia variant. In 21 of 35 patients soluble receptor levels were also monitored during and after recombinant interferon-alpha therapy. Clinical and hematological parameters were also assessed. Soluble interleukin-2 receptor levels were extremely high at the time of diagnosis in patients with typical hairy-cell leukemia [32,722 +/- 27,001 vs. 331 +/- 145 units/ml in controls (mean +/- SD)], but not in patients with the leukemia variant. A progressive decrease in soluble interleukin-2 receptor levels paralleled the clinical response to treatment, although normal values were never detected, even in patients who achieved an apparent complete remission. After recombinant interferon-alpha discontinuation, disease recurrence was accompanied by a progressive increase to pre-treatment soluble receptor levels. Overall, a close correlation was found between soluble interleukin-2 receptor values and total tumor burden (r = 0.84, P < 0.001). On the basis of these data, soluble interleukin-2 receptor should be regarded as a key marker in the management of patients with hairy-cell leukemia.