Serum levels of CD8 antigen and soluble interleukin 2 receptors in patients with B cell chronic lymphocytic leukemia

We assayed the plasma levels of CD8 antigen (CD8Ag) and soluble interleukin 2 receptor (sIL-2R) in 34 subjects with B cell chronic lymphocytic leukemia (B-CLL) and in 15 controls using an immunoenzymatic method. The results showed higher average levels of soluble CD8 (sCD8) and sIL-2R in the leukemic patients compared to the controls (sCD8 = 860 vs. 306 U/ml; sIL-2R = 4,131 vs. 311 U/ml). The two antigen levels were significantly higher in patients with progressive disease than in those with indolent disease, and they also correlated with Rai's stage. sIL-2R levels correlated with lymphocyte count (p less than 0.001), while there was no correlation between sCD8 levels and total number of lymphocytes. These results seem to show that the measurement of serum levels of CD8Ag and sIL-2R may be a useful tool in the prognostic evaluation of patients with B-CLL.     

Increased serum levels of soluble IL-2 receptor, CD30 and CD8 molecules, and gamma-interferon in angioimmunoblastic lymphadenopathy: possible pathogenetic role of immunoactivation mechanisms

Abnormal immunoreaction associated with increased cell activation phenomena might play a role in the pathogenetic events leading to the development of angioimmunoblastic lymphadenopathy (AILD). In the present study we investigated the serum levels of some soluble molecules related to cell activation in 24 patients with AILD at presentation. In particular, we measured by immunoenzymatic or immunoradiometric techniques the levels of the Tac peptide (sIL-2R), soluble CD30 (sCD30) and CD8 (sCD8) antigens, and gamma-IFN (gIFN). The results show that all the above molecules are increased as compared to normal controls, with a different pattern of increase for the different molecules. The sIL-2R levels were very high in all cases with no overlap between AILD and control samples (mean 6315 +/- 3374 U/ml, controls 271 +/- 112 U/ml, P less than 0.001). Very high values of the sCD30 antigen (722 +/- 895 U/ml) were detected in all cases but five, as opposed to the lack of detectable levels in controls. A significant increase of sCD8 (978 +/- 646 U/ml, controls 334 +/- 95 U/ml, P less than 0.01) and gIFN (329 +/- 236 U/ml, controls 97 +/- 43 U/ml, P less than 0.01) was also observed with some overlap between AILD samples and controls. The above findings further support the view that a condition of abnormally enhanced cell activation is likely to play a central role in the pathogenetic events leading to the composite clinicopathological picture of AILD.     

Short communication: decreasing soluble CD30 and increasing IFN-gamma plasma levels are indicators of effective highly active antiretroviral therapy

It was previously reported that without highly active antiretroviral therapy (HAART), secretion of Th1 cytokines and antiviral IFN-gamma in HIV-infected patients is decreased, whereas the production of Th2 cytokines, proinflammatory cytokines, and TNF-alpha is increased. We studied the effect of HAART on Th1-, Th2-, and monocyte-derived cytokines, and on the Th2-type immune response marker soluble (s)CD30 in HIV-1-infected hemophilia patients. Viral Load (VL), CD4+ lymphocyte counts, and plasma levels of sIL-1RA, IL-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-7, IL-10, TNF-alpha, TGF-beta2, IFN-gamma, and sCD30 were measured in 18 patients who received HAART. Nine patients were initially treatment-naive and were monitored after the initiation of HAART. sCD30 median levels were significantly higher in treatment-naive patients than in patients who were on HAART (77 vs. 30 U/ml, p = 0.005). A strong association was observed between sCD30 and VL (r = 0.85, p = 0.004). After the initiation of HAART, sCD30 levels decreased and remained low (at 1 year, 38; at 2 years, 41 U/ml; p = 0.012 and p = 0.021, respectively, as compared to baseline level) and this was accompanied by a decrease in VL and monocyte-derived IL-6 and an increase in CD4+ lymphocyte counts and Th1-derived IFN-gamma. One year after the initiation of HAART a strong inverse correlation was observed between IFN-gamma and VL (r = -0.83, p = 0.006). In contrast to sCD30 and IFN-gamma, CD4 counts and plasma IL-6 did not correlate with VL at any time. Our data suggest that decreasing sCD30 and increasing IFN-gamma plasma levels are indicators of effective HAART treatment and CD4 Th1 cell recovery in HIV-infected patients.     

Effect of Fuzheng Yiliu decoction combined with chemotherapy on patients with intermediate and late stage gastrointestinal cancer

AIM: To investigate the therapeutic effects of Fuzheng Yiliu (strengthening the body resistance to inhibit tumor) decoction combined with chemotherapy on the patients with intermediate and late stage gastrointestinal cancer. METHODS: Sixty patients were randomly divided into treatment group (chemotherapy combined with Fuzheng Yiliu decoction) and control group (chemotherapy alone). Four indexes, including the tumor recent remission rate (RR), the change of main symptoms, the toxic and side effects caused by chemotherapy and the change of performance status, were observed in the patients. Peripheral blood contents of CD3+, CD4+, CD8+ cells, CD4+/CD8+ and soluble interleukin-2 receptor (sIL-2R) were tested before and after treatment and the values were compared with those of healthy peoples. RESULTS: The improving rate of main symptoms (69.6%) and performance status (56.7%) were significantly higher in the treatment group than in the control group (34.8%, 26.7%, P<0.05). The occurrence rates of grade II toxic and side-effects on both bone marrow (13.3%) and digestive tract (30%) were lower in the treatment group compared to the control group (36.7%, 63.3%, P<0.05). Before treatment, the proportion of CD3+, CD4+ and CD4+/CD8+ decreased and the proportion of CD8+ and SIL-2R raised markedly both in the control group and treatment group as compared to the healttiy people. After treatment, that increased of CD3+, CD4+, CD4+/CD8+ increased (62.25±10.01% vs 68.31±9.72%, 36.83±10.44% vs 42.6±9.62%, 1.24±0.65 vs l.66±0.85, P<0.05) and the values of CD8+ and sIL-2R decreased obviously (33.06±7.69% vs 29.24±6.25%, 588.23±216.86 U/mL vs 475.87±211.36 U/mL,P<0.05) in the treatment group, whereas these values were opposite in the control group (64.22±6.91% vs60.63±5.75%,35.62±7.49% vs31.53±5.53%, 32.95±8.28% vs 37.14±7.48%, 1.17±0.43 vs 0.94±0.43, 573.63±214.32 U/mL vs 692.17?21.33 U/mL, P<0.05). CONCLUSION: Fuzheng Yiliu decoction can enhance therapeutic effects of chemotherapy on malignant gastrointestinal tumor, and also reduce the toxic and side effects on bone marrow and digestive tract, thereby improving the quality of life and cellular immunity in patients with malignant gastrointestinal tumor.     

Clinical implications of increased plasma levels of CD8 in patients with hairy cell leukemia

Plasma levels of soluble T-suppressor/cytotoxic antigen (sCD8) were measured at diagnosis or before systemic treatment in 69 patients with hairy cell leukemia (HCL). The 49 nonsplenectomized patients were characterized by high concentrations of sCD8 antigen as compared with 17 controls (P less than .0001). The median sCD8 level in non- splenectomized patients was 1,050 U/mL (range: 160 to 2,400 U/mL) and was significantly higher (P less than .0001) than the median of 275 U/mL (range: 20 to 1,080 U/mL) in splenectomized patients. The relationship of sCD8 to clinical response to subsequent interferon alpha (IFN alpha) treatment was analyzed. Patients who showed subsequent hematologic response with normalization of all blood counts had significantly lower levels of sCD8 concentrations at diagnosis than those who did not (P = .0056). Furthermore, normalization of sCD8 during IFN alpha treatment paralleled the achievement of normal counts in peripheral blood, whereas soluble interleukin-2 receptor (sIL-2R) levels remained high in most patients after 12 to 15 months of treatment. We speculate that activation of suppressor/cytotoxic T cells might play a role in myelosuppression, and its modulation during treatment with IFN alpha correlates with normalization in peripheral blood counts.     

大骨节病患者淋巴细胞亚群及sIL-2R的检测意义

目的　探讨大骨节病患者外周血淋巴细胞分布形式、血清可溶性白细胞介素 - 2受体 (s IL- 2 R)及其与硒的相关性。方法　在大骨节病病区随机选取经 X线和临床检查确诊的大骨节病儿童 ,同时在该病区和非病区分别选取健康儿童作为对照组。采用单克隆抗体 (抗 CD4 ,CD8)免疫细胞组化法检测淋巴细胞亚群。s IL- 2 R的测定采用双抗体夹心 EL ISA法。结果　大骨节病病区儿童外周血单核细胞 (PBMC)中 CD4 +、CD8+率显著低于非病区水平 (P <0 .0 5 ) ,CD4 / CD8各组间没有差异 (P >0 .0 5 )。患儿组血清 s IL- 2 R水平显著高于非病区水平 (P =0 .0 38)。病区健康儿童组较非病区有升高趋势 ,但差异无显著意义。另外 ,病区儿童红细胞硒水平仍显著低于非病区 (P <0 .0 0 1)。相关分析表明 ,红细胞硒水平与 CD4 +率呈典型正相关 (r=0 .6 2 5 ,P <0 .0 5 ) ,与血清 s IL-2 R水平则无明显相关关系。结论　大骨节病病区儿童外周血处于一种免疫抑制状态 ,以 CD4 + 、CD8+ 比例的减少尤为明显。硒通过影响 PBMC中 T淋巴细胞亚群的分布形式从而在这种免疫紊乱中发挥了重要作用。建议把血清 s IL - 2 R的测定作为检出大骨节病儿童的一种参考指标。     

Immune function in patients with acute pancreatitis

BACKGROUND: The aim of this study was to clarify the relationship between the balance of T-helper (Th)1 and Th2 cytokines, and the numbers of CD4+ T and CD8+ T-cells, and was investigated, together with the plasma concentration of the antigen, an apoptosis marker, in patients with mild and acute pancreatitis (AP). METHODS: Plasma concentrations of soluble (s) CD4, sCD8, sIL-2-R, IL-12, IFN-gamma and sFas antigen were measured by ELISA, and CD4+ T, and CD8+ T lymphocyte counts were measured by flow cytometry. RESULTS: Both CD4+ T and CD8+ T-cells were reduced in number; in the severe cases the reduction in the former was more pronounced. A significant positive correlation was noted among the concentrations of sCD4, sIL-2-R and IL-12, and a significant positive correlation was also found between sCD4 and sFas. During the early stage of AP, the concentrations of sCD4, sCD8, sIL-2-R, IL-12 and IFN-gamma increased more in the severe cases compared with those who had milder symptoms; however, these increases were moderated during the clinical course. CONCLUSION: We considered that these Th1 type CD4+ T cells probably induce the activation of macrophages and further pro-inflammatory reactions during the early stage of AP, as well as exerting direct cytotoxicity effects through Fas/Fas ligand expression.     

Detection of soluble IL-2 receptor in the serum of patients with myelodysplastic syndromes: induction under therapy with GM-CSF

Sera of 15 healthy controls and 33 patients suffering from myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) expression with a cell-free enzyme-linked immunosorbent assay (ELISA) system (T-Cell Sciences; Cambridge, U.S.A.). The upper limit of the assay is indicated with 477 U/ml. According to the FAB classification eight refractory anaemia (RA), 15 refractory anaemia with excess of blasts (RAEB), five refractory anaemia with excess blasts in transformation (RAEBt) and five chronic myelomonocytic leukaemia (CMML) were examined. None of the patients had reported infectious episodes or been under treatment with cytotoxic agents and/or cytokines within the previous 3 months. Significant differences in sIL-2R levels between RA (median 368 U/ml). RAEB (median 675 U/ml) and RAEBt (median 971 U/ml) and between RA and CMML (median 723 U/ml) were detected. Six patients, who had been under treatment with rhGM-CSF for at least 2 weeks, demonstrated a three- to sevenfold increase of sIL-2R expression compared to pretreatment levels. In kinetic evaluation of serum samples for 24 h, the increase of sIL-2R expression begins within 4 h after subcutaneous application of GM-CSF and reaches its maximum after 12 h. Our data cannot suggest whether increased sIL-2R expression is a primary event due to involvement of lymphocytes in the malignant clone or whether it results from secondary alteration of the cytokine network. Application of GM-CSF in MDS may result in improvement of altered lymphocyte function. As GM-CSF induces sIL-2R expression, a down regulation of the immune response caused by neutralization of free IL-2 cannot be excluded.     

Clinical significance of serum soluble interleukin-2 receptor level in patients with non-Hodgkin's lymphoma]

The aim of this study was to assess the clinical significance of serum soluble interleukin-2 receptors (sIL-2R) in non-Hodgkin's lymphoma (NHL). Using a sandwich ELISA method, serum sIL-2R levels were measured in 720 samples from 87 patients with NHL (including 65 untreated patients) and 36 patients with other diseases such as infectious mononucleosis. The mean serum sIL-2R level in NHL was 4,017 U/ml (mean +/- SD, 4017 +/- 6352 U/ml). Patients in clinical stages III/IV (5116 +/- 6629) had significantly higher sIL-2R levels than those in clinical stages I/II (813 +/- 611). Patients with sIL-2R levels exceeding 8,000 U/ml had significantly lower survival rates (2-year survival: 12.3%) than those with sIL-2R levels below 8,000 U/ml (2-year survival: 76.0%) (P < 0.01). Multivariate analysis of variables including age, clinical stage, LDH, CRP, performance status, number of extranodal diseases, and sIL-2R demonstrated that sIL-2R and LDH were significant prognostic indicators of overall survival. The upper limit of the 95% confidence interval for maximum sIL-2R level in follow-up of patients with complete remission was 2,014 U/ml. Although an increased sIL-2R level of around 2,000 U/ml in the remission stage did not necessarily suggest relapse of NHL, it did seem to warrant careful follow-up. The serum sIL-2R level appears to reflect tumor activity and may prove to be a useful prognostic indicator in patients with NHL.     

Soluble CD4, CD8 in patients with polymyositis/dermatomyositis

Summary The concentrations of soluble CD4 (sCD4) and soluble CD8 (sCD8) were determined in 64 patients with polymyositis/dermatomyositis (PM/DM). The patients with PM/DM had significantly higher concentrations of sCD8, though the concentrations of sCD4 did not significantly increase. Patients with high concentrations of sCD8 tended to have too high concentrations of soluble interleukin-2 receptor (sIL-2R). The patients with high levels of myogenic enzymes tended to have high concentrations of sCD8. The results of a serial study indicated that the concentrations of sCD8 decreased simultaneously with the decrease of the myogenic enzymes. These results may suggest that the activation of CD8⁺ cells are related to muscular involvement.     

Serum soluble interleukin-2 receptor measurement in patients with sarcoidosis: a clinical evaluation

OBJECTIVES: To date, insufficient evidence is available to recommend serum soluble interleukin-2 receptor (sIL-2R) measurement as a routine test in the assessment of sarcoidosis. Therefore, we evaluated the clinical value of this test. DESIGN: Forty-seven patients with sarcoidosis, all presenting with active disease, were included in the study. Initial serum sIL-2R levels were determined by enzyme-linked immunosorbent assay, and clinical data at presentation and follow-up were collected retrospectively. RESULTS: The median follow-up period of all patients was 44 months (range, 6 to 100 months), and 38 patients had follow-up data present over at least 24 months. The median sIL-2R level was 1,068 U/mL (range, 248 to 4,410 U/mL; upper limit of normal, 710 U/mL). A positive correlation was found between serum sIL-2R levels and the number of CD4+ T lymphocytes in BAL (rs = 0.53, p < 0.001). In accordance with this result, both sIL-2R level and the number of CD4+ T lymphocytes were elevated in stage I compared to stage III disease (p < 0.05). Patients with extrapulmonary disease (ED) [excluding L?fgren's syndrome] showed higher sIL-2R levels than those presenting with only pulmonary sarcoidosis (p = 0.001). No relation was found between sIL-2R level and response to treatment, and there was no association between sIL-2R levels and radiographic evolution and lung function outcome. CONCLUSIONS: Our data suggest a role for serum sIL-2R as marker of pulmonary disease activity and ED in patients with sarcoidosis.     

Soluble intercellular adhesion molecule-1 (ICAM-1), CD4, CD8 and interleukin-2 receptor in patients with Beh?et's disease and Vogt-Koyanagi-Harada's disease.

OBJECTIVES: In a search for serum markers of disease activity in uveitis, we measured the levels of the soluble form of ICAM-1 (sICAM-1), CD4 (sCD4), CD8 (sCD8) and interleukin-2 receptor (sIL-2R) in the serum of patients with Beh?et's disease (BD) and Vogt-Koyanagi-Harada's disease (VKH). METHODS: The study population consisted of 20 patients with active BD (treated with tacrolimus), 15 patients with inactive BD, 24 patients with VKH [20 of them successfully treated with systemic corticosteroids (cured group) and 4 of them with two or more episodes of uveitis after withdrawal of systemic steroid (recurrence group)], and 20 normal individuals. The levels of serum sICAM-1, sCD4, sCD8 and sIL-2R were measured by sandwich ELISA. RESULTS: Sera from patients with BD in the convalescent stage showed significantly higher levels of sICAM-1 than those in the acute stage. Patients with active BD in both stages or VKH in the acute stage had significantly higher levels of serum sCD4 and sIL-2R than the controls. The levels of sCD8 in patients with both diseases in both stages differed significantly compared to the controls. No difference was noted in the pattern of decline of these soluble markers after treatment in the cured and recurrence groups of VKH patients. A positive correlation was found between the serum levels of sCD4 and sIL-2R in patients with both diseases in the acute stage. CONCLUSIONS: The results suggest that these soluble markers may represent potentially useful parameters to monitor disease activity or chronic inflammation in certain types of autoimmune uveitis.     

CD69, CD25, and HLA-DR activation antigen expression on CD3+ lymphocytes and relationship to serum TNF-alpha, IFN-gamma, and sIL-2R levels in aging

Aging is associated with changes in lymphocyte subsets and unexplained HLA-DR upregulation on T-lymphocytes. We further investigated this activation, by measuring early (CD69), middle (CD25), and late (HLA-DR) T-lymphocyte activation markers on CD3+ lymphocytes, across subjects (20-100 years) together with serum tumor necrosis factor (TNF-alpha), interferon-gamma (IFN-gamma), and soluble interleukin-2 receptor (sIL-2R). HLA-DR was present as a CD3+ HLA-DR+ subset that constituted 8% of total lymphocytes, increased twofold with age and included CD4+, CD8+, and CD45RA+ phenotypes. HLA-DR was also expressed on a CD8+ CD57+ subset. The CD3+ CD25+ subset constituted 13% of lymphocytes, fell with age but was weakly associated with the CD3+ HLA-DR+ subset especially in older subjects. A small 3-5% CD3+ CD69+ subsets showed no age effect. Serum sIL-2R, TNF-alpha, but not IFN-gamma, were associated with CD3+ HLA-DR+ lymphocytes, TNF-alpha with CD8+ CD57+ count and sIL-2R and IFN-gamma with the CD3+ CD25+/CD3+ CD4+ ratio. The study confirms age-related upregulation of HLA-DR on CD3+ lymphocytes, shows some evidence for associated upregulation of CD25 on CD3+ cells in older subjects, and links serum TNF-alpha, IFN-gamma, and sIL2-R to T-lymphocyte activation.     

Elevated serum-soluble interleukin-2 receptor levels in patients with anaplastic large cell lymphoma

Levels of serum soluble interleukin 2 receptor (sIL-2R) provide a reliable marker of disease activity in patients with hairy cell leukemia and adult T-cell leukemia/lymphoma. The malignant cells in patients with anaplastic large cell lymphoma (ALCL) express CD30 and are usually positive for expression of CD25. We measured serum sIL-2R and soluble CD30 (sCD30) levels in patients with ALCL treated with EPOCH (etoposide, prednisone, Oncovin, Cytoxan, hydroxydaunorubicin) infusional chemotherapy. Serum sCD30 levels were elevated and decreased in response to therapy as previously reported. Serum sIL-2R levels were elevated in 7 of 9 patients with ALCL and decreased in response to treatment. Baseline serum sIL-2R levels varied but correlated well with serum sCD30 levels (r = 0.97). Patients positive for the anaplastic lymphoma kinase (ALK) gene showed elevated sIL-2R levels, whereas those negative for ALK had normal serum sIL-2R levels and their tumors lacked CD25 expression. Serum sIL-2R levels were elevated in both patients with recurrent disease.     

Granulocyte-colony-stimulating factor induces increased serum levels of soluble interleukin 2 receptors preceding engraftment in autologous bone marrow transplantation

Summary The serum levels of soluble interleukin 2 receptors (sIL-2R) were determined in 19 patients who received highdose chemotherapy and an autologous or syngeneic bone marrow transplant (BMT) for treatment of Hodgkin's disease ( n = 18) or non-Hodgkin's lymphoma ( n = 1). Twelve patients received granulocyte colony-stimulating factor (G-CSF) from day 0 or day +1 after autologous BMT until the white blood cell count had been stable for 9 d above 1 × 10⁹/1, the remaining seven patients did not receive growth factors, In all G-CSF-treated patients the sIL-2R levels increased steadily in the early post-transplant course, even in the absence of infection. This increase was statistically significant 2-4 d prior to the appearance of leucocytes in the peripheral blood (median 340 pm versus median 256 pm immediately after BMT, P <0.025) and peaked with the appearance of first peripheral blood leucocytes (median 536 pm, P <0.001). Cessation of G-CSF administration resulted in a decline of sIL-2R levels. In contrast, five of seven patients without G-CSF treatment did not exhibit an sIL-2R increase before or at the time of engraftment. Infection was associated with a rise of sIL-2R levels. A correlation between sIL-2R levels and total leucocyte count, lymphocyte count, or CD25 + lymphocyte count was not evident.
These data suggest that after autologous BMT G-CSF induces increased sIL-2R levels, which occur independent of lymphocyte activation. This may be compatible with involvement of immature bone marrow cells in G-CSF-induced sIL-2R release.     

Serum-soluble interleukin-2 receptor (sIL-2R) level determines clinical outcome in patients with aggressive non-Hodgkin’s lymphoma: in combination with the International Prognostic Index

Purpose The aim of the present study was to assess the prognostic significance of serum soluble interleukin-2 receptor (sIL-2R) in aggressive non-Hodgkins lymphoma (NHL).Methods One hundred and thirteen consecutive patients with previously untreated aggressive NHL (diffuse large B-cell lymphoma, 96; peripheral T-cell lymphoma, 17) prospectively participated in this study between 1995 and 2001. The patients were treated with 6–8 cycles of a CHOP or THP (pirarubicin)-COP regimen.Results A high serum sIL-2R level (2,000 U/ml and over) at onset was associated with a low complete remission rate. Patients with high sIL-2R had significantly lower survival rates (5-year, 24%) than those with low sIL-2R (under 2,000 U/ml) (74%) (P<0.01). Multivariate analysis employing sIL-2R levels and conventional prognostic factors demonstrated that high sIL-2R, presence of B-symptoms, and advanced age (60 years and older) were significantly unfavorable variables for overall survival. In addition, we attempted to use sIL-2R in combination with the International Prognostic Index (IPI). The patients in the high (H) risk group and those with high sIL-2R in the low-intermediate (LI)/high-intermediate (HI) risk group had significantly lower survival rates than the patients in the low (L) risk group and those with low sIL-2R in the LI/HI risk group (P<0.001).Conclusion The results suggest that a high serum sIL-2R level predicts a poor prognosis in aggressive NHL and may be a useful biomarker for selecting appropriate treatment when used in combination with the IPI.     

A high serum-soluble interleukin-2 receptor level is associated with a poor outcome of aggressive non-Hodgkin's lymphoma

Soluble interleukin-2 receptor (sIL-2R) is produced by activated T and B cells, and the level of this receptor is elevated in patients with non-Hodgkin's lymphoma (NHL). The present study demonstrated that the sIL-2R level was high in the following groups of patients with aggressive NHL; those aged > or = 60 yr, those with a poor PS, those in Ann Arbor stage III or IV, and those in the high intermediate or high risk group according to the International Prognostic Index (IPI). Overall survival was significantly poorer when the sIL-2R level was 2000 U/ml or more. In addition, the overall survival of patients in the low (L) and low-intermediate (L-I) risk groups with an sIL-2R level of 3000 U/ml or more was significantly poorer, suggesting that the sIL-2R level could be particularly useful for identifying patients with a poor prognosis among the L and L-I risk groups. Univariate analysis identified some significant prognostic factors, and multivariate analysis of these factors plus the five IPI prognostic factors showed that the sIL-2R level was an independent prognostic indicator. In conclusion, the present findings established that the sIL-2R level is a significant independent prognostic factor in patients with aggressive NHL.     

Elevated serum-soluble interleukin-2 receptor (Tac antigen) levels in chronic myelogenous leukemia patients with blastic crisis

We examined the expression of cell-surface interleukin-2 (IL-2) receptor (Tac antigen) on peripheral blood leukemic cells and measured soluble IL-2 receptor p55(alpha) chain (sIL-2R) levels in sera from chronic myelogenous leukemia (CML) patients with blastic crisis. Flow cytofluorometric analysis performed by dual immunofluorescence in three cases demonstrated coexpression of Tac antigen with myeloid (CD13, CD14, or CD33) or lymphoid (CD10) antigen on significant proportions of peripheral blood leukemic cells. Radiolabeled IL-2-binding assay demonstrated the specific IL-2 binding sites in three cases examined. The exogenous IL-2, however, failed to induce proliferative response. A myeloid cell line, Yut-K3, established from peripheral blood leukemic cells from a CML patient with blastic crisis, also expressed cell- surface Tac antigen and CD13 concurrently. SIL-2R assay showed that Yut- K3 released a detectable amount of sIL-2R in its culture supernatant. The serum sIL-2R levels were significantly elevated (range: 2,580 to 172,000 U/mL) in 12 CML patients with blastic crisis and were slightly elevated in ten patients in chronic phase (range: 250 to 820 U/mL) and in three in accelerated phase (range: 790 to 1,305 U/mL) compared with those in 24 normal controls (range: 70 to 695 U/mL, P less than .01). These results indicated that the leukemic cells from CML patients with blastic crisis expressed and released IL-2 receptor (Tac antigen). Longitudinal studies performed in three cases of CML with blastic crisis showed that the change of serum sIL-2R level was closely associated with that of the number of peripheral blood leukocytes and blasts, the percentage of blasts and serum LDH levels, also suggesting that the serum sIL-2R level is a useful clinical indicator of the leukemic cell burden in vivo.     

High Plasma Levels of the Soluble Form of CD30 Activation Molecule Reflect Disease Activity in Patients with Wegener's Granulomatosis

PURPOSE: To determine the plasma levels of soluble CD30 (sCD30) in Wegener's granulomatosis (WG) patients, and to investigate the possible correlation of sCD30 with disease extent and activity.PATIENTS AND METHODS: sCD30 was determined by radioimmunoassay in 57 WG patients, 25 patients with rheumatoid arthritis (RA), 23 patients with bacterial infections and 21 healthy controls (HC). The extent and activity of WG disease were assayed according to disease extent index (DEI) and standard laboratory parameters.RESULTS: Plasma sCD30 levels in generalized WG (22.5 ± 1.5 U/mL), but not in initial phase WG (12.1 ± 4.0 U/mL), were significantly increased compared with HC (8.8 ± 0.9 U/mL, P < 0.0001). Furthermore, of 11 generalized WG patients who received long-term follow-up, sCD30 levels declined when the disease activity changed from active disease to remission (29.1 ± 1.9 U/mL to 15.9 ± 1.8 U/mL, P = 0.0001). Similar results were observed in the whole group of generalized WG, eg, sCD30 levels in active disease (29.4 ± 1.4 U/mL) were significantly higher than in partial remission (17.9 ± 1.9 U/mL, P < 0.001) and in complete remission (13.7 ± 3.3 U/mL, P < 0.001). No significant difference was noted between complete remission and HC. Inaddition, sCD30 levels were correlated with other parameters of disease extent and activity such as DEI, plasma levels of sIL-2R, PR3-ANCA, ESR and CRP. The sCD30 levels were increased in RA patients compared with HC (15.2 ± 2.1 U/mL, P < 0.05), but no correlation was found between disease activity patameters and sCD30 levels. In contrast, in patients with bacterial infections sCD30 levels (6.9 ± 0.9 U/mL) were not significantly different compared with HC.CONCLUSION: Plasma levels of sCD30 are not only significantly increased but also correlate with disease extent and activity in generalized WG. These findings suggest that sCD30 can act as a useful marker for evaluation of disease extent and activity, and that generalized WG may be associated with Th2-type immune response.     

Levels of soluble CD8 antigen and circulating immune complexes in intravenous drug abusers: relationships to HIV antibody serology

A total of 36 intravenous drug abusers (IVDA) were studied for circulating immune complexes (CIC) and serum soluble CD8 antigen (sCD8). None had symptoms or signs of AIDS-related complex or AIDS. sCD8 levels were significantly higher in 18 patients who had HIV antibody (Ab) compared with 18 patients who were HIV Ab negative (1640 +/- 578 virus 804 +/- 264 U/ml, p less than 0.0001). In HIV Ab+ patients but not in HIV Ab- patients, sCD8 levels significantly correlated with percentages and absolute numbers of activated CD3+DR+ peripheral blood mononuclear cells (p = 0.0024 and 0.0183, respectively). Also in HIV Ab+ patients, CIC levels were significantly greater for both anti-C3 binding (13.1 +/- 11.1 versus 2.9 +/- 3.4 micrograms/ml, p = 0.002) and C1q binding (23.5 +/- 20.2 versus 6.3 +/- 4.3 micrograms/ml, p = 0.001) CIC. Serum C4 concentrations were lower in the HIV Ab+ patient group (33.9 +/- 10.1 versus 41.6 +/- 12.4 mg/dL, p = 0.043). In the seropositive group, IgG levels were higher (2206 +/- 859 versus 1615 +/- 645 mg/dl) and total CD4 cell counts were lower (757 +/- 344 versus 1172 +/- 402 cells per mm3), but at a less significant level (p = 0.024 and 0.005, respectively), than that seen for sCD8 and C1q CIC differences. These results suggest that elevations of both the lymphocyte activation marker sCD8 and antigen nonspecific CIC characterize earlier stages of HIV infection in IVDA.