Serum thymidine kinase and soluble interleukin-2 receptor predict recurrence of malignant lymphoma

Before and after therapy, serum thymidine kinase (TK) and soluble interleukin-2 receptor (sIL-2R) were serially determined in 28 patients with malignant lymphoma (ML). In 15 patients achieving and maintaining complete remission (CR) for more than 2 years, serum TK and sIL-2R were unchanged or decreased gradually. In contrast, logarithmic linear increases of TK and sIL-2R were observed in 13 relapsed patients. The increments of the serum markers occurred more than 10 months before the relapse. A significant positive correlation between the slope of the line for TK and that for sIL-2R was noted. The doubling time for TK estimated from the slope also showed a positive correlation with that for sIL-2R. Taken together, serum TK and sIL-2R were shown to be quite sensitive and interrelated serum markers for the recurrence of ML. Slopes of logarithmic linear increase, which are proper and specific for the individual patients, are inversely correlated with the doubling time and reflect proliferation of ML. We conclude that serum TK and sIL-2R are better predictors of relapse than LDH and the international prognostic index (IPI).     

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.     

Clinical study on soluble interleukin-2 receptor in patients with sarcoidosis]

Levels of soluble IL-2 receptor in sera of 18 patients with sarcoidosis were measured by a sandwich ELISA method established by the authors and were found to be significantly higher than those in sera of normal subjects. Levels of soluble IL-2 receptor in sera of sarcoidosis cases of bilateral hilar lymphadenopathy (BHL) were significantly higher than those in sera of sarcoidosis cases without BHL. In patients with sarcoidosis, levels of soluble IL-2 receptor did not differ in relation to the presence or absence of ocular lesions, or in relation to positive or negative response to protein purified derivative of tuberculosis (PPD).     

Pancreatic T-cell lymphoma with high level of soluble interleukin-2 receptor

An 82-year-old man was admitted to hospital with symptoms of abdominal fullness and loss of appetite. Abdominal computed tomography (CT) scan and ultrasonography showed enlargement of the whole pancreas with para-aortic lymphadenopathy. Endoscopic retrograde pancreatography (ERP) showed diffuse narrowing of the main pancreatic duct (MPD), and brushing cytology from the MPD was non-neoplastic. Differential diagnosis between lymphoma and other exocrine and endocrine pancreatic malignancies was needed, and the level of serum soluble interleukin-2 receptor (17 751 U/ml) was revealed to be significantly high, which was strongly suggestive of pancreatic lymphoma. Chemotherapy was refused by the patient's family and the patient succumbed after 2 months of conservative follow-up. Autopsy revealed diffuse, mixed cell-type, non-Hodgkin's lymphoma of T-cell subtype.     

Prognostic value of the soluble interleukin-2 receptor level after patients with follicular lymphoma achieve a response to R-CHOP

Objectives: Follicular lymphoma (FL) is a clinically and biologically heterogeneous disease. Therefore, it is important to identify factors that can predict its clinical outcome.

Methods: We retrospectively evaluated the usefulness of soluble interleukin-2 receptor (sIL-2R) levels after R-CHOP (posttreatment sIL-2R) in 72 patients with newly diagnosed FL who had either a complete response (CR) or partial response. With the use of a recursive partitioning analysis, we determined the cut-off values of post- and pretreatment sIL-2R levels that were associated with disease progression, which corresponded to 486.5 and 5405?U/mL, respectively.

Results: The high posttreatment sIL-2R group showed a significantly inferior progression-free survival (PFS) compared to the low posttreatment sIL-2R group in all patients (3-year PFS 52.6% vs. 77.4%, P?=?0.003), and in patients with CR (3-year PFS 57.1% vs. 82.1%, P?=?0.034). Although a multivariate analysis showed that pretreatment sIL-2R, but not posttreatment sIL-2R, was an independently significant predictive factor for disease progression, among patients with low pretreatment sIL-2R levels, those with high posttreatment sIL-2R levels tended to have inferior PFS. There was a significant trend in PFS among the high pretreatment sIL-2R group, the low pre- and high posttreatment sIL-2R group, and the low pre- and low posttreatment sIL-2R group (P?Conclusion: Among patients with a low pretreatment sIL-2R level who exhibited a positive response to R-CHOP, the posttreatment sIL-2R level may help to identify those with a poor prognosis.     

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.     

Plasma soluble interleukin-2 receptor in patients with primary myelofibrosis

Summary Using an enzyme-linked immunosorbant assay (ELISA) test, the level of soluble Tac peptide, one chain of the human interleukin-2 receptor, was measured in the plasma of 26 patients with primary myelofibrosis (MF), seven patients with polycythaemia vera and 11 normal controls. The plasma soluble interleukin-2 receptor (sIL-2R) was found to be significantly elevated in patients with primary MF compared to polycythaemia vera or controls ( P <0·01), while the plasma sIL-2R of patients with polycythaemia vera also was found to be significantly elevated compared to controls ( P <0·01). The significantly elevated value of sIL-2R seen in primary MF may be secondary to T cell activation resulting from autoimmune phenomena, and myeloblast activation with release of sIL-2R may also be a contributing factor. In primary MF, plasma sIL-2R levels were also found to be correlated to survival, circulating blast cell counts, and thrombocytopenia, but not to white blood cell counts, LDH levels, degree of marrow fibrosis, or degree of splenomegaly. Patients with primary MF with higher titre of plasma sIL-2R had a shorter survival. Further studies involving more patients and longer follow-up may substantiate that plasma sIL-2R is an important prognostic indicator in primary MF.     

Neopterin and a soluble interleukin-2 receptor in patients with systemic lupus erythematodes

Goal of this study was to monitor levels of serum neopterin and soluble interleukin-2 receptor (sIL-2r) and to evaluate their importance in monitoring activity of systemic lupus erythematodes (SLE). Levels of serum neopterin, anti-dsDNA antibodies, C3, C4 complement components, nucleosomes antibodies, IL-10, fas ligand, soluble thrombomodulin, sVCAM-1, and sICAM-1 were measured in a group of 52 patients with SLE. Positive correlations were proved between neopterin concentrations and disease activity (ECLAM), levels of sVCAM-1, sICAM-1, sIL-2r and thrombomodulin, further between sIL-2r level and disease activity (ECLAM), and concentrations sVCAM-1, sICAM-1 and neopterin. Higher values of neopterin and sIL-2r levels were identified in patients with lupus nephritis compared to patients without kidney impairment. Statistically significant differences were identified in levels of neopterin between a subgroup (A) with minimum disease activity and a subgroup (B) with increasing disease activity (p = 0.01) and a subgroup (C) with decreasing disease activity (p = 0.003 ) and a subgroup (LN) with lupus nephritis (0.007) during the first and the third series of measurements. sIL2r levels which had in all subgroups very varied values were the lowest in the subgroup A with minimum disease activity during the whole time of monitoring. The highest levels reached the free receptor IL-2 in the subgroup B with increasing disease activity and in the subgroup with lupus nephritis. Statistically significant differences in values were identified between the subgroup A (non-active) and the subgroup LN (lupus nephritis) with p = 0.01 during the first set of the measurements. Fluctuation of sIL-2r levels in individual subgroups during the time of monitoring did not reach statistically important levels. In conclusion it could be said that potential practical utilization of the measurement of concentrations of the two mentioned molecules should be seen especially in monitoring disease activity because they don't contribute to SLE with needed information. Their always low values have favourable prognostic impact in monitoring patients with SLE and vise versa.     

Triiodothyronine enhances expression of the interleukin-2 receptor alpha chain.

The effect of thyroid hormone on immune function is unclear. The influence of L-triiodothyronine on expression of the interleukin-2 receptor alpha chain by peripheral blood mononuclear cells from healthy volunteers and YT cells (an interleukin-2 independent natural killer-like cell line) was examined. Concanavalin A stimulation significantly (p<0.05 and p<0.01) increased soluble interleukin-2 receptor alpha chain production when mononuclear cells were cultured with triiodothyronine (1-100 nmol/l) for 3 days. The stimulatory effect of triiodothyronine on interleukin-2 receptor alpha chain expression was greater in the presence of concanavalin A (5 microg/ml) plus interleukin-2 (1 U/ml) than in the presence of concanavalin A alone. Triiodothyronine also significantly (p<0.01) increased interleukin-2 receptor alpha chain expression when YT cells were cultured for 2 days with interleukin-2 (1 U/ml), but did not influence receptor expression when YT cells were cultured with forskolin or 12-O-tetradecanoyl phorbol 13-acetate, potent activators of signal transduction. In conclusion, triiodothyronine may have an immunomodulatory effect by enhancing expression of the interleukin-2 receptor alpha chain on peripheral blood mononuclear cells in the presence of interleukin-2.     

乙型肝炎后肝硬化患者血清可溶性白介素-2受体水平的变化

目的　了解肝炎后肝硬化患者血清可溶性白介素 2受体 (sIL 2R)水平的变化及其与肝炎活动的相关性。方法　采用酶联免疫法测定 3 7例乙型肝炎后肝硬化患者血清sIL 2R水平。结果　乙型肝炎后肝硬化患者血清sIL 2R水平显著增高 (P <0 0 1) ,并与血清丙氨酸转氨酶水平呈正相关 (r =0 3 8,P <0 0 5 )。结论　检测血清sIL 2R对了解免疫功能状态以及判断病情有一定价值     

Acute myeloid leukaemia relapsing following interleukin-2 treatment expresses the alpha chain of the interleukin-2 receptor

Immunotherapy with recombinant human Interleukin-2 (rhIL-2) was given to nine patients in first complete remission from acute myeloid leukaemia (AML). Five patients relapsed. The median time to relapse after commencing rhIL-2 was 26 weeks (range 2-44). Four patients were studied at relapse. The morphological and cytochemical features at relapse and presentation were similar. Cytogenetic analysis at relapse in patients 1 and 3 showed a normal karyotype. At relapse, patient 4 had the abnormality 46,XY, t(2;3). Patient 2 had the chromosomal abnormality t(8;21) at presentation and relapse. Patients 3 and 4 with M5 AML relapsed rapidly at 2 and 9 weeks after starting rhIL-2 treatment. Relapse leukaemia cells had features normally associated with lymphoid development. Patient 3 was TdT positive, with rearranged immunoglobulin genes, and a proportion of cells expressing the CD7 antigen; patient 4 also expressed the CD7 antigen. Relapse leukaemic cells from three of four patients expressed the alpha chain of the IL-2 receptor as assessed by flow cytometry. After overnight incubation and removal of T-lymphocytes the proportion of cells from these patients expressing the alpha chain increased from 15% to 61% (P less than 0.01). Using tritiated thymidine uptake to assess cell proliferation, two of three patients who expressed the IL-2 receptor alpha chain proliferated in response to 1000 u/ml of rhIL-2 in vitro, with a stimulation index greater than 1.95 (P less than 0.05). Following rhIL-2 immunotherapy for AML, relapse cells may express an inducible form of the alpha chain of the IL-2 receptor, which can mediate a proliferative response. It is possible that rhIL-2 when administered to AML patients in remission, may induce relapse. This may be a particular risk in patients with the M5 subtype.     

Serum soluble interleukin-2 receptor in patients with pulmonary mycobacterial diseases]

Serum soluble interleukin-2 receptor (sIL-2R) levels were measured in patients with untreated pulmonary tuberculosis (24 cases), patients with multidrug-resistant intractable pulmonary tuberculosis (7 cases) and patients with pulmonary non-tuberculous mycobacteriosis (27 cases). Serum sIL-2R levels were elevated in patients with pulmonary mycobacterial diseases and were elevated in untreated pulmonary tuberculosis patients than in other patients. In patients with new tuberculosis, serum sIL-2R levels were higher in patients with extensive lesions. Serum sIL-2R level showed significant positive correlation with serum C-reactive protein level and erythrocyte sedimentation rate, and significant negative correlation with serum albumin level. In patients with intractable tuberculosis and patients with non-tuberculous mycobacteriosis, serum sIL-2R levels were lower than in patients with new tuberculosis. Even in patients with extensive lesions, serum sIL-2R levels were not elevated. Lower levels of serum sIL-2R, marker of immunocompetent cell activity, suggested that immunocompetent cell activity was suppressed in intractable tuberculosis and in non-tuberculous mycobacteriosis.     

Plasma soluble interleukin-2 receptor levels in patients with idiopathic thrombocytopenic purpura

Soluble interleukin-2 receptor (sIL-2R) was measured in the plasma of 31 patients with idiopathic thrombocytopenic purpura (ITP) and 22 normal controls. When thrombocytopenia persisted longer than 6 months, the diagnosis of chronic ITP was made. Twenty patients had acute ITP, 11 patients had chronic ITP, and all patients received high-dose methylprednisolone (HDMP) (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days). The sIL-2R levels of the patients were determined before being giving HDMP and 14 days after the end of HDMP therapy. Platelet counts were determined before administration of HDMP, one day after the end of HDMP therapy, and once every 28 days for 7 months thereafter. There was not a significant difference between the mean pre-treatment plasma sIL-2R levels of both acute and chronic ITP groups (P > 0.05), and these were higher than that of the control group (P < 0.001). The mean post-treatment sIL-2R level of the chronic ITP group was significantly higher than those of both the control and post-treatment acute ITP groups (P < 0.001). There were negative correlations between the plasma sIL-2R levels and platelet counts of both group patients in the pre-treatment period and between post-treatment sIL-2R levels and platelet counts in chronic ITP group (P < 0.05). We think that there was a good correlation between prognosis of ITP and sIL-2R levels after HDMP therapy, and platelet counts in patients with ITP are linked to sIL-2R levels. Am. J. Hematol. 57:119–123, 1998. © 1998 Wiley-Liss, Inc.     

Interleukin-6, soluble interleukin-2 receptor and soluble interleukin-6 receptor in the sera of patients with different histological patterns of rheumatoid synovitis

OBJECTIVE: The present study was conducted to investigate whether the serum levels of interleukin 6 (IL-6), soluble IL-2 receptor (sIL-2R) and sIL-6R are associated with the morphological appearance of rheumatoid arthritis (RA). METHODS: Using the ELISA technique we measured the IL-6, sIL-2R and sIL-6R concentrations in the serum of 34 patients with RA and 28 patients with osteoarthritis (OA). Histological analysis of synovial samples distinguished 2 types of rheumatoid synovitis. Twenty-one RA specimens presented diffuse infiltrates of mononuclear cells without any specific microanatomical organization. In remaining 13 samples the formation of lymphocytic follicles with germinal center-like structures was found. RESULTS: Serum levels of IL-6, sIL-2R and sIL-6R were elevated in patients with RA compared to the OA control group (p < 0.001, p < 0.001 and p < 0.05 respectively). Concentrations of IL-6 and sIL-2R were highest in the serum of RA patients with follicular synovitis in comparison to patients with diffuse synovitis (p < 0.001 and p < 0.01 respectively) and could distinguish RA patients with these two histological variants of the disease. Serum levels of IL-6 and sIL-2R correlated with markers of disease activity such as ESR and CRP levels. In addition, the clinical data suggest a more severe disease among RA patients with follicular synovitis. CONCLUSION: Distinct histological types of rheumatoid synovitis associated with unique serum concentrations of IL-6 and sIL-2R reflect levels of disease activity and confirm the concept of RA heterogeneity.     

Serum soluble interleukin-2 receptor in eosinophilia

The relationship between soluble interleukin-2 receptor (sIL-2R) levels and clinical characteristics was evaluated in patients with eosinophilia. Thirty-eight out of 60 patients showed sIL-2R levels of more than 800 U/ml. In these patients, sIL-2R was closely related to the eosinophil count, but not the IgE level. Their underlying diseases were heterogeneous, including neoplasms and collagen diseases. In patients with lower sIL-2R levels, there was no relationship to the eosinophil count, but sIL-2R was correlated with the IgE level. These findings indicate that patients with eosinophilia and higher sIL-2R levels tend to have underlying diseases other than allergy, and might be more severely ill than patients with lower sIL-2R levels. sIL-2R may be a good marker for evaluating patients with eosinophilia, as an indicator of the probable etiology and severity of their diseases.     

支气管哮喘患者血浆可溶性白介素-2受体水平与气道炎症关系的研究

目的 探讨支气管哮喘患者血浆中可溶性的白介素2受体(soluble interleukin-2 receptor,sIL-2R)和气道黏膜的炎症程度的关系.方法 采用ELISA 法检测15例哮喘患者和15例健康对照者血浆中sIL-2R,并对支气管黏膜活检标本的炎症细胞定量计数.结果 哮喘患者血浆中sIL-2R水平明显高于正常对照组[(47.47±13.29) U/ml,(31.59±4.00) U/ml,P<0.05].哮喘患者的血浆sIL-2R水平与支气管上皮层内嗜酸粒细胞数呈正相关(rs＝0.82,P<0.05),与炎症细胞总数呈正相关(rs＝0.75,P<0.05).结论 sIL-2R与哮喘气道炎症相一致,可用于监测气道炎症的活动性.     

支气管哮喘患者血浆可溶性白介素-2受体水平与气道炎症关系的研究

目的探讨支气管哮喘患者血浆中可溶性的白介素2受体(soluble interleukin-2 receptor,sIL-2R)和气道黏膜的炎症程度的关系。方法采用ELISA法检测15例哮喘患者和15例健康对照者血浆中sIL-2R,并对支气管黏膜活检标本的炎症细胞定量计数。结果哮喘患者血浆中sIL-2R水平明显高于正常对照组(47.47±13.29)U/mlvs(31.59±4.00)U/ml,(P<0.05)。哮喘患者的血浆sIL-2R水平与支气管上皮层内嗜酸粒细胞数呈正相关(rs=0.82,P<0.05),与炎症细胞总数呈正相关(rs=0.75,P<0.05)。结论sIL-2R与哮喘气道炎症相一致,可用于监测气道炎症的活动性。     

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.