sCD30 Concentration Research Articles

Extracellular CD30 and ADAM10/17 Regulate Brentuximab Vedotin-Induced Cell Death in an Adult T-Cell Leukemia Cell Line

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus 1 (HTLV-1)-induced malignancy of mature T lymphocytes with poor outcomes. Brentuximab vedotin (BV), which is an anti-CD30 antibody conjugated with monomethyl auristatin E, is included in the treatment of CD30-positive ATL, but there is no useful therapeutic marker for BV. Soluble CD30 (sCD30) in serum is increased in aggressive-type ATL at diagnosis, but the effects of extracellular CD30 on BV-induced cell death in ATL remain unclear. Similarly, a disintegrin and metalloproteinase (ADAM) 10 and 17 have CD30 sheddase activity in anaplastic large cell lymphoma, but this activity is unknown in ATL. The present study showed that sCD30 concentrations were related to BV activity in ATL-related cell lines. Extracellular vesicles (EVs) such as exosomes containing CD30 also inhibited BV activity. Additionally, the knockdown of ADAM10/17 significantly reduced sCD30 concentrations with increased cell death by BV. Our results suggest that ADAM10/17 are involved in sCD30 production in ATL. Moreover, endogenous extracellular CD30, such as sCD30 shed by ADAM10/17, and CD30-positive EVs may be responsible for the BV-induced cell death. Correctively, extracellular CD30 concentrations, including EV, may be useful as biomarkers for BV therapy in ATL.

Cerebrospinal fluid CXCL10 is associated with the presence of low level CSF HIV during suppressive antiretroviral therapy

Surrogate markers of HIV central nervous system (CNS) persistence are needed because direct HIV measurements from the CNS require specialized protocols and are not always detectable or quantifiable. We analyzed paired plasma and CSF samples from people with HIV (PWH) on suppressive therapy (ART) with a validated HIV single copy RNA assay. Two potential markers of CNS persistence were measured (CXCL10 and sCD30). We then examined associations with CSF HIV RNA positivity in univariable and multivariable analyses. Among 66 individuals, 18.2% had detectable CSF HIV. Individuals who had detectable HIV in CSF had higher CSF CXCL10 concentrations (median 514 pg/ml versus median 317 pg/ml, p = 0.019), but did not have significantly different CSF sCD30 concentrations (median 7.5 ng/ml versus median 7.6 ng/ml, p = 0.78). In the multiple logistic analysis, both higher CSF CXCL10 (p = 0.038) and plasma HIV detectability (p = 0.035) were significantly associated with detectable CSF HIV. Both sCD30 and CXCL10 correlated positively with NfL and NSE, two neuronal markers. This study demonstrates that CSF CXCL10 concentrations reflect low level HIV CNS persistence despite virologic suppression on ART. Given that it is readily detectable and quantifiable, this chemokine may be a promising biomarker to evaluate HIV eradication therapies that target the CNS.

Decline in Total Serum IgE and Soluble CD30 in the Context of Soil-Transmitted Helminth Decline in Bolivia.

In the Bolivian Chaco, recent surveys documented a dramatic decrease in the prevalence of soil-transmitted helminth (STH) infections as compared with the 1980s after thirty years of preventive chemotherapy (PC). Concomitant immunological rearrangements are expected. Because nematode infections are associated with increased levels of circulating IgE and glycoprotein CD30 soluble form (sCD30), this study aims to evaluate changes in serological markers of T helper (Th)2-cells activity between 1987 (high STH prevalence) and 2013 (low STH prevalence) in rural communities in the Bolivian Chaco area. We collected 151 sera during two different surveys in 1987 (n = 65) and 2013 (n = 86) and measured the concentration of total IgE and sCD30 by immunoassays. We found a statistically significant age-independent decrease in the total IgE (P < 0.0001) and sCD30 (P < 0.0001) from 1987 to 2013. The significant decrease in serological Th2 markers (IgE and sCD30) between 1987 and 2013 is consistent with the drop in STH prevalence in this geographical area during the same period of time. Further studies might elucidate the clinical and epidemiological impact of these serological rearrangements.

Levels of Soluble CD30 and CD26 and Their Clinical Significance in Patients with Primary Immune Thrombocytopenia.

Background sCD30 and sCD26 are correlated with autoimmune diseases. However, little research has been done on the relationship between them and primary immune thrombocytopenia (ITP). Methods This study enrolled 47 patients diagnosed with ITP in the Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences (Tianjin, China), from January 2015 to August 2015. The peripheral blood of all subjects was collected. The mRNA expression of CD30 was quantified by RT-PCR, and concentrations of sCD30 and sCD26 were measured by ELISA. Patient characteristics, CD30 mRNA levels, and sCD30 and sCD26 concentrations were analyzed. Results The concentration of sCD30 was higher in active ITP patients (median, 35.82 ng/mL) than in remission ITP patients (median, 23.12 ng/mL; P = 0.021) and healthy controls (median, 25.11 ng/mL; P = 0.002). Plasma sCD26 levels decreased in remission ITP patients compared with that in healthy controls (median, 599.4 ng/mL vs. 964.23 ng/mL; P = 0.004). Ratios of sCD26/sCD30 in active ITP patients decreased compared with those in controls (P = 0.005). Increased sCD30 was positively correlated with hemorrhage (r = 0.493, P = 0.017) in ITP patients while little relationship was identified between sCD26 and ITP. Conclusion Since sCD30 levels and sCD26/sCD30 ratios may contribute to the activity of the disease, they may be used to assess ITP disease activity.

Immunological Alterations due to Hemodialysis Might Interfere with Early Complications in Renal Transplantation.

Background Chronic or intercurrent alterations of the immune system in patients with end-stage renal disease (CKD) and intermittent hemodialysis (CKD5D, HD) have been attributed to an acute rejection of renal allograft. Methods Leukocyte subsets in flow cytometry, complement activation, and concentrations of TGFβ, sCD30 (ELISA), and interleukins (CBA) of fifteen patients eligible for renal transplantation were analyzed before, during, and after a regular HD. Results Before HD, the median proportion of CD8+ effector cells, CD8+ CCR5+ effector cells, and HLA-DR+ regulatory T cells as well as the median concentration of soluble CD30 increased and naive CD8+ T cells decreased. During HD, there was a significant decrease in CD4- CD8- T cells (p < 0.001) and an increase in CD25+ T cells (p = 0.026), sCD30 (p < 0.001), HLA-DR+ regulatory T cells (p = 0.005), and regulatory T cells (p = 0.003). TGFβ and sCD30 increased significantly over time. The activity of the classical complement pathway started to slightly increase after the first hour of HD and lasted until fifteen minutes after finishing dialysis. The decrease in the functional activity of the alternative pathway was only transient and was followed by a significant increase within 15 minutes after finishing the treatment. Conclusion HD might interact with the allograft outcome by influencing T cell subsets and activation of the complement system in a biphasic course.

Clinical significance of tryptophan catabolism in Hodgkin lymphoma.

Indoleamine 2,3‐dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly diagnosed Hodgkin lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 concentration. The IDO expression was evaluated in the patients’ affected lymph nodes. The cohort comprised 22 male and 30 female patients (age range, 15‐81 years; median, 45 years), with a 5‐year overall survival (OS) of 88.6%. The OS was significantly shorter for patients with a high Kyn/Trp ratio (OS at 5 years, 60.0% vs 92.2%), for those with stage IV disease, and for those with lymphocytopenia (<600/mm3 and/or <8% white blood cell count). The latter two parameters are components of the international prognostic score for advanced HL. In contrast, there were no significant differences in OS according to age, serum albumin, hemoglobin, sex, white blood cell count, or serum soluble CD30 (≥ or <285.6 ng/mL). Multivariate analysis using the three variables stage, lymphocytopenia, and serum Kyn/Trp ratio showed that only the latter significantly affected OS. Indoleamine 2,3‐dioxygenase 1 was produced by macrophages/dendritic cells, but not by HL tumor cells, and IDO levels determined by immunohistochemistry had a significant positive correlation with the serum Kyn/Trp ratio. In conclusion, quantification of serum Kyn and Trp is useful for predicting prognosis of individual HL patients.

Dynamics of Soluble B-Cell Activation Markers sCD27 and sCD30 and Risk of B-Cell Lymphoma: A Prospective Study Using Repeated Plasma Samples Donated up to 25 Years Pre-Diagnosis

Background: We studied changes in blood concentrations of the soluble B-cell activation markers sCD27 and sCD30 in relation to future lymphoma risk, by investigating repeated pre-diagnostic plasma samples from the same individuals. High levels of sCD27 and sCD30 have been associated with lymphoma risk in previous prospective studies based on a single pre-diagnostic blood sample per participant. These studies, however do not inform about the dynamics of the marker-disease association on an individual level hampering its interpretation and potential use in lymphoma diagnostics and disease monitoring.Methods: In the Northern Sweden Health and Disease Study cohort we identified 170 individuals who had donated two pre-diagnostic blood samples and subsequently developed B-cell lymphoma. Blood samples were donated 13.2±4.4 and 5.5±4.0 years (mean±SD) prior to diagnosis, respectively. Cancer-free controls from the same cohort were individually matched to cases on a 1:1 ratio on sex, age and blood draw dates. We investigated associations between lymphoma risk by subtypes and marker concentrations; as measured separately at baseline, at time of the repeated sample, as well as the association with rate of change (slope) while adjusting for the baseline marker concentration.Findings: We observed strong associations between B-cell lymphoma risk and sCD27 and sCD30 concentrations, both at baseline and at time of the repeated blood sample. Associations were evident in samples collected up to 25 years before diagnosis. Blood concentrations of sCD27 and sCD30 increased significantly closer to diagnosis among future B-cell lymphoma cases, while they remained temporally stable among controls. Modeling measures of baseline and slope simultaneously with multivariable conditional logistic regression to estimate odds ratios (ORs), revealed significant associations between both slope and baseline measures and lymphoma risk; sCD27 (ORBaseline=7.2, Ptrend=2.8 x 10-4; ORSlope=2.8, Ptrend=2.2 x 10-4), and sCD30 (ORBaseline=2.9, Ptrend=3.7 x 10-4; ORSlope=2.9, Ptrend=0.001) (ORs 4th vs. 1st quartile; P for linear trend based on median values of analyte quartiles used as a continuous variable). Subtype specific analyses showed that the association between lymphoma risk and slope was restricted to indolent subtypes and mainly driven by chronic lymphocytic leukemia; sCD27 (ORSlope=6.7, Ptrend=1.3 x 10-5), and sCD30 (ORSlope=5.9, Ptrend=4.8 x 10-5), while associations with baseline marker concentration were evident among different subtypes, including diffuse large B-cell lymphoma.Interpretation: B-cell lymphoma risk seems to be influenced by increased sCD27 and sCD30 blood concentrations more than two decades before diagnosis. Increased concentrations of these B-cell activation markers among different future lymphoma subtypes early in life may reflect a constitutional predisposition, suggesting a role of B-cell activation in lymphoma development at early stages across subtypes. The observed increase of sCD27 and sCD30 concentrations closer to diagnosis however, seems to be subtype-specific and restricted to indolent lymphoma cases. Therefore, these markers may reflect early progression of undiagnosed disease and could potentially be utilized to improve lymphoma diagnostics and disease monitoring in indolent lymphoma. DisclosuresNo relevant conflicts of interest to declare.

O2-8-5 - Possible stimulatory immune checkpoint molecules releasing allows adult T-cell leukemia/lymphoma development

The interleukin (IL)-2 receptor α chain (IL-2Rα, CD25) and CD30 are cell membrane proteins expressed on activated T-cell. High levels of soluble cytokine receptors, soluble IL-2Rα (sIL-2R) and soluble CD30 (sCD30) are detected in the serum of patients with adult T-cell leukemia/lymphoma (ATL), which is a highly aggressive leukemia/lymphoma caused by human T-cell leukemia virus type 1 (HTLV-1) (Nishioka C, Takemoto S, et al. 2005; Porunkuna R, Takemoto S, et al. 2014). Freshly isolated leukemic cells from acute type ATL patients express little CD30 on the surface, and predominantly produce sCD30 (Pornkuna R, Nishioka C, and Takemoto S. 2014). We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers (Takemoto S, et al. 2015). We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sIL-2R and sCD30 concentrations at baseline were significantly higher in cases than in controls (P = 0.009 and P<0.001, respectively). In the univariate logistic regression analysis, a higher sIL-2R (≥546.5 U/mL) or sCD30 (≥30.2 U/mL) was significantly associated with ATL development. Among cases, sIL-2R and sCD30 concentrations tended to increase at the time of diagnosis of aggressive-type ATL, but the concentrations were stable in those developing the smoldering-type. High levels of sIL-2R probably down-regulate the proliferative capability of T cells that encounter tumor cells, and proliferating ATL cells are thought to release sCD30, and excess sCD30 may block CD30L on normal activated T cells and myeloid cells, protecting CD30+ ATL cells from apoptosis. Accordingly, high levels of sIL-2R and sCD30 suggest that impaired tumor surveillance leads to the survival of ATL cells. The interleukin (IL)-2 receptor α chain (IL-2Rα, CD25) and CD30 are cell membrane proteins expressed on activated T-cell. High levels of soluble cytokine receptors, soluble IL-2Rα (sIL-2R) and soluble CD30 (sCD30) are detected in the serum of patients with adult T-cell leukemia/lymphoma (ATL), which is a highly aggressive leukemia/lymphoma caused by human T-cell leukemia virus type 1 (HTLV-1) (Nishioka C, Takemoto S, et al. 2005; Porunkuna R, Takemoto S, et al. 2014). Freshly isolated leukemic cells from acute type ATL patients express little CD30 on the surface, and predominantly produce sCD30 (Pornkuna R, Nishioka C, and Takemoto S. 2014). We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers (Takemoto S, et al. 2015). We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sIL-2R and sCD30 concentrations at baseline were significantly higher in cases than in controls (P = 0.009 and P<0.001, respectively). In the univariate logistic regression analysis, a higher sIL-2R (≥546.5 U/mL) or sCD30 (≥30.2 U/mL) was significantly associated with ATL development. Among cases, sIL-2R and sCD30 concentrations tended to increase at the time of diagnosis of aggressive-type ATL, but the concentrations were stable in those developing the smoldering-type. High levels of sIL-2R probably down-regulate the proliferative capability of T cells that encounter tumor cells, and proliferating ATL cells are thought to release sCD30, and excess sCD30 may block CD30L on normal activated T cells and myeloid cells, protecting CD30+ ATL cells from apoptosis. Accordingly, high levels of sIL-2R and sCD30 suggest that impaired tumor surveillance leads to the survival of ATL cells.

YKL-40 Gene Expression and Plasma Levels of CD30 are not Affected by Isoflurane or Propofol: Pilot Study

Background: It has been hypothesized that the body's response to anesthesia techniques can increase risk of cancer recurrence and metastatic disease after surgery and also can modulate immune responses. Some acute inflammatory markers have been measured to survey the immunomodulatory effect of anesthesia, but in this research, we studied the plasma level of CD30 and YKL-40 gene expression which can present major changes of the immune system. M aterials and Methods: Our study was a controlled before and after study . 34 women with biopsy-proven breast cancer were randomized to receive either propofol general anesthesia (n=17) or standard isoflurane general anesthesia (n=17). There were no significant differences between the two patient groups in age, body weight, and height, length of general anesthesia, operative time and group of surgery. The blood samples were collected in two different sets, before anesthesia and 72-h postoperatively. Soluble CD30 (sCD30) plasma level was measured by ELISA and YKL-40/CHI3L1 gene expression was evaluated by real-time-PCR. Results : The results showed that the anesthetics, propofol and isoflurane, have no effect on the expression of YKL-40. Despite increased in the expression of YKL-40 that was observed in patients receiving isoflurane, this increase was not statistically significant. There was no significant increase or decrease in plasma concentrations of sCD30. C onclusion: YKL-40 and sCD30 are not affected by isoflurane or propofol. So, in immunological perspective, there is no preference in use of isoflurane or propofol in breast cancer patients.

Soluble B-cell activation marker of sCD27 and sCD30 and future risk of B-cell lymphomas: A nested case-control study and meta-analyses.

Prediagnostic serum/plasma concentrations of B-cell activation markers have been associated with future risk of B-cell lymphomas (BCL) in HIV-infected patients and in the general population. Current evidence for the general population is however limited and relies on relatively small numbers of observations, especially for specific histologies. We carried out a nested case-control study, including 218 BCL and 218 matched controls, within two prospective cohorts, to investigate the association between plasma levels of soluble (s)CD27 and sCD30 and future risk of BCL, and main histologic subtypes separately. To expand the evidence further, we performed meta-analyses of the published data on these associations from prospective studies among the general population. Our study revealed a significant relationship between sCD30 concentration and BCL risk (OR = 0.86, 1.53, 1.76, for the 2nd-4th quartiles respectively, p trend = 0.01). Similar increased risks were observed for diffuse large B-cell lymphoma and follicular lymphoma. Analyses of sCD27 blood concentrations did not show significant associations with BCL, (OR = 0.90, 1.26, 1.65 for the 2nd-4th quartiles, respectively, p trend = 0.17), but significant associations were observed for chronic lymphocytic leukaemia and for the group of "other BCL" subtypes. Our findings involving sCD30 were confirmed within our meta-analyses of five prospective cohorts, while results were more heterogeneous for sCD27 with the exception of CLL which was found consistently in all studies. Data to date suggest that chronic B-cell stimulation might be an important mechanism involved in B-cell lymphomagenesis both in HIV-infected and in the general population.

Selected immunological parameters in clinical evaluation of patients with atopic dermatitis.

IntroductionIt has been suggested that soluble immune receptors (SIRs) such as sCD25 and sCD30 may serve as potential biomarkers in evaluation of atopic dermatitis (AD). Previous studies clearly indicated that serum levels of interleukin (IL)-13 and total IgE (tIgE) might be potentially useful in the evaluation of patents with AD.AimTo evaluate whether serum levels of sCD25 and sCD30 are suitable biomarkers of AD. Moreover, we have decided to estimate the usefulness of tIgE and IL-13 serum level determination in the evaluated population.Material and methodsA group of 102 AD patients was investigated. Serum concentrations of sCD30, sCD25, IL-13 and tIgE were measured. The clinical phenotype of AD was classified as extrinsic (ADe) or intrinsic (ADi) based on the presence of IgE. Statistical analysis was performed to estimate correlations between obtained results and clinical features of the population such as AD phenotype, age, disease extent and severity.ResultsExtrinsic AD was diagnosed in 71% of patients, while ADi phenotype was observed in 29% of the investigated population. A negative correlation between serum levels of sCD25 and sCD30 and disease severity as well patients’ age was established. Serum levels of IL-13 did not reach the cut-off point set by the manufacturer. A positive correlation between serum levels of total IgE and disease severity and patients’ age was observed.ConclusionsThis paper shows that serum levels of sCD25 and sCD30 as well as tIgE are age dependent. Determination of serum levels of sCD25, sCD30 and IL-13 is not useful in everyday practice.

Adult T-cell leukemia/lymphoma following elevation of serum levels of soluble cytokine receptors, sCD25 and sCD30

Adult T-cell leukemia /lymphoma (ATL) caused by human retrovirus, HTLV-1, is a neoplasm of mature T-cell. ATL is still an incurable disease with approximately 1,000 annual deaths in Japan. The useful biomarkers are required to achieve the success of treatment. In order to test whether or not two soluble cytokine receptors (sCD25 and sCD30) are useful biomarkers of the development of ATL, we investigated changes in the concentration of the two markers in 11 HTLV-1 carriers (pre/post ATL progression) and six patients with chronic ATL (pre/post acute crisis). Serum (or plasma) samples of newly diagnosed or referred ATL patients and HTLV-1 carriers were preserved in freezer to measure the level of soluble proteins, sCD25 and sCD30, using ELISA. The sCD25 concentration was measured by Cell freeN IL-2R (Kyowa Medex, Japan) and Determiner CL IL-2R (Kyowa Medex, Japan). The sCD30 concentration was measured by Human sCD30 Platinum ELISA (eBioscience). The probability of ATL development from HTLV-1 carrier state was analysed by Kaplan-Meier method. We found that the elevation of soluble cytokine receptors was one of the earlier events of ATL development. In addition, chronic type patients followed in our hospital showed sCD30 as well as sCD25 elevation prior to the diagnosis of acute crisis. Our findings suggest that a combination of sCD25 and sCD30 facilitates accurate diagnosis and intervention of ATL as useful biological markers. Further careful follow-up should be required for HTLV-1 carriers with elevated level of cytokine receptors, sCD25 and sCD30 to diagnose the early phase of ATL.

SCD30 and sCD40L detection in patients with osteosarcoma, chondrosarcoma and Ewing sarcoma.

Primary malignant bone tumors are heterogeneous groups of neoplasms, which affect mainly children and adolescents. The most common types are Osteosarcoma, Ewing sarcoma and chondrosarcoma. Elevation of sCD30 and sCD40L has been observed in lymphoma, leukemia and autoimmune disorders. To evaluate serum concentrations of sCD30 and sCD40L in patients with primary malignant bone tumors. Fifty-four cases (31 Osteosarcomas, 14 Ewing sarcomas, and 9 Chondrosarcomas) and 54 healthy controls enrolled in this study. Cases with the history of prior treatment (surgery, chemotherapy and radiotherapy) were excluded from the study. Serum levels of sCD30 and sCD40L were detected by an enzyme linked immunosorbent assay (ELISA). Mean serum concentration of sCD30 in Ewing sarcoma was significantly higher than that of the control groups (p=0.007), but mean serum concentrations of sCD30 in osteosarcoma and chondrosarcoma groups were not significantly different, compared to the controls (p=0.41 and p=0.11, respectively). Mean serum concentrations of sCD40L in osteosarcoma, Ewing sarcoma and chondrosarcoma groups were significantly higher than that of the control group (p<0.0001). In addition, the mean serum level of sCD40L in chondrosarcoma patients was higher than that of both Ewing sarcoma and osteosarcoma groups (p<0.001). sCD30 and sCD40L increase in primary bone tumors; however the significant of these findings for diagnosis or prognosis of these tumors needs further investigation.

Soluble CD30 and ELISA-detected human leukocyte antigen antibodies for the prediction of acute rejection in pediatric renal transplant recipients

Biomarker-based post-transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well-controlled prospective randomized trial was analyzed pre- and post-transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T-cell reactivity, and anti-human leukocyte antigen (anti-HLA) antibody reactivity, a biomarker for B-cell activation. A sCD30 concentration ≥40.3U/ml on day 14 was able to discriminate between patients with or without biopsy-proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut-off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut-off (P=0.004). For pre- and post-transplant anti-HLA class II reactivities by enzyme-linked immunosorbent assay, a cut-off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti-HLA reactivities. An increased post-transplant sCD30 serum concentration and positive pre- and post-transplant anti-HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG-506-02-43).

Soluble CD30 in normal pregnancy, pre-eclampsia and recurrent pregnancy loss.

Normal pregnancy is thought to be dependent on Th2 deviation, while Recurrent Pregnancy Loss (RPL) and Pre-eclampsia (PE) appear to be biased toward the Th1 immune response. It is believed that the soluble form of CD30 (sCD30) is an index of Th2 immune response or modulator of Th1/Th2 responses. The aim of this study was determination of the sCD30 level in RPL and PE patients. The sCD30 level was measured in sera of a group of normal non-pregnant women (N=43) and compared with normal pregnancy at the first (N=42) and third (N=42) trimester. Furthermore, the level of sCD30 in the normal first and third trimester pregnancies were compared with that of RPL (N=38) and severe pre-eclamptic (N=41) patients, respectively. sCD30 levels were measured by ELISA method and student t-test was used for statistical analysis. The mean level of sCD30 at the first trimester in normal pregnancy was significantly elevated as compared with normal non-pregnant women (21.4 vs. 15.2 ng/ml, p<0.0001). A significant difference between sCD30 concentration at the first and third trimester of normal pregnancies was also observed (21.4 vs. 14.3 ng/ml, p<0.0001). Interestingly, the sCD30 concentration did not show any significant changes at the first trimester of normal pregnancy as compared with RPL (21.4 vs. 20.9 ng/ml) and third trimester of normal pregnancy as compared with PE (14.3 vs. 13.1 ng/ml). The data of this study indicated that the concentration of sCD30 in serum during pregnancy period is not associated with RPL or PE and serum sCD30 is not a good correlate of Th2 immune responses in pregnancy.

Imbalance in serum soluble CD30/CD30L and CD40/CD40L systems are associated with ovarian tumors

The aim of the study was to examine the concentrations of the soluble receptors and their ligands of CD30/CD30L and CD40/CD40L systems in the serum of women with ovarian tumor and in the ovarian cyst fluid of women with Cystadenoma serosum. The study included 120 women with ovarian tumors. As a control, sera were obtained from 60 healthy female volunteers. Concentrations of the sCD30, sCD30L, sCD40 and sCD40L in the serum and the ovarian cyst fluid were measured by ELISA enzyme-linked immunosorbent assay. Concentrations of both sCD30 and sCD30L in serum of women with ovarian tumors were significantly higher than in control (p < 0.0001). The highest serum receptor and its ligand levels were observed in women with ovarian cancer (p < 0.0001). Moreover, results showed significantly increased levels of sCD40 and sCD40L serum in women with ovarian tumors, as compared to the control group (p < 0.0001). The highest concentration of sCD40 in the serum of women with ovarian cancer and sCD40L in serum of women with Teratoma maturum (p < 0.0001) were observed. Impaired apoptosis among women with ovarian tumors is associated with the impairments of soluble CD30/CD30L and CD40/CD40L systems. Measurement of studied parameter concentrations in serum of women with ovarian tumors has been suggested to be a potential tool in monitoring of inflammatory. Evaluation of sCD30, sCD30L and sCD40 might be an early diagnostic marker in patients with the ovarian cancer. Concentrations of the studied parameters in the ovarian cyst fluid higher than the serum values suggest local suppression of the immune response. However, the final evaluation of the importance of measurement of serum levels of them requires further investigation.

P065 Acute crisis of adult T-cell leukaemia following soluble CD30 elevation: Shedding of CD30 and CD25 from cell surface associated with the aggressiveness

Introduction Adult T-cell leukaemia/lymphoma (ATL) caused by human retrovirus, HTLV-1, is a neoplasm of mature T-cell. In Japan, more than a thousand patients with ATL die every year because this disease still remains incurable. Acute crisis is a common phenomenon of chronic leukaemia and indolent haematological malignancy, in which proliferation of leukaemic cells is accelerated following a certain term of chronic phase. Although some genetic changes are thought to be responsible for this sudden change of characteristics in leukaemic cells, it has been unclear if they are the cause or the result of crisis. Methods We assessed the therapy and outcome of 79 newly diagnosed or referred ATL patients from 2005 to 2010. Serum sample of patient was preserved in freezer to measure the level of soluble proteins, sCD30 and sIL-2R, using ELISA. The sIL-2R concentration in serum was measureed by Cell freeN IL-2R (Kyowa Medex, Japan) and Determiner CL IL-2R (Kyowa Medex, Japan). The sCD30 concentration in serum was measured by Human sCD30 Platinum ELISA (eBioscience). In the present study, patients with ATL chronic type were investigated by monitoring changes in the serum levels of sIL-2R and sCD30. Results Six patients showed acute crisis from chronic phase (the observed periods of chronic phase are 31–866 days) and increasing sCD30 level as well as sIL-2R elevation was found as an earlier event of the acute crisis (average levels of sCD30 and sIL-2R were 2029 U/ml and 14035 U/ml in acute crisis; 341 U/ml and 5008 U/ml in chronic phase). In contrast, average of sCD30 and sIL-2R in 25 HTLV-1 carriers are 37 U/ml and 428 U/ml, respectively. Although the patterns and levels of soluble proteins elevation were unique to each case, serum sCD30 level predominantly elevated at the crisis. Interestingly, CD30 is not always detected on the surface of ATL cells. Chronic inflammation caused by constituvive activation of STATs may be associated with Matrix Metalloproteinase activation which sheds CD30 from the surface of ATL cells. Conclusion Our findings suggest that soluble protein levels in sera of patients are useful biological markers for diagnosis and therapy of ATL. Furthermore, since spontaneous remission was observed during the insufficinet level of serum sCD30 by comparison to the sIL-2R level, it is conceivable that the sCD30 protects CD30+ leukaemic stem cells from CD30 ligand-mediated cell death.

Serum and CSF soluble CD26 and CD30 concentrations in healthy pediatric surgical outpatients

Activated T-helper type 1 (Th1) lymphocytes induce a cellular type immune response, and Th2 lymphocytes, a humoral or antibody-mediated type immune response. Soluble CD26 (sCD26) and soluble CD30 (sCD30) are regarded as markers of Th1 and Th2 lymphocyte activation, respectively. Serum from 112 generally healthy pediatric surgical patients and cerebrospinal fluid (CSF) from 39, aged 1-17 years were measured for sCD26 and sCD30 using an enzyme-linked immunosorbent assay method. The detection limit for sCD26 was 6.8 ng/ml and for sCD30, 1.9 IU/ml. For serum sCD26 and sCD30, 2.5% and 97.5% percentiles constituted the reference limits, and the 95% credible intervals for the percentiles were calculated using regression models with a Bayesian approach. A significant between-gender difference was observed (P = 0.015) in serum sCD26 concentration, of which the lower limits ranged between 273 and 716 ng/ml for girls and 235 and 797 ng/ml for boys. The upper limits ranged between 1456 and 1898 ng/ml for girls and between 1419 and 1981 ng/ml for boys. Moreover, the concentrations of sCD26 increased in infants and children up to 10 years in girls and 12 years in boys. After this however, the values decreased. The serum sCD30 concentration was highest among the youngest infants aged 1 year (80-193 IU/ml), after which a consistent age-related decrease was found. The lowest values were found at the age of 17 years (10-89 IU/ml). A significant between-gender difference in sCD30 concentration was observed (P = 0.019). sCD26 and sCD30 concentrations were low in the CSF samples analyzed: 13.3 ng/ml (median); range 8.3-51.5 ng/ml and 7.6 IU/ml; 2.1-18.5 IU/ml, respectively. Reference limits for serum sCD26 in children aged 1-17 years were established as being 235-1800 ng/ml in toddlers and 400-1800 ng/ml in female adolescents and 700-2000 ng/ml in male adolescents. For sCD30; reference limits of 80-190 IU/ml were established in the youngest age group and 10-90 IU/ml in adolescents.

Circulating Soluble CD30 and Future Risk of Lymphoma; Evidence from Two Prospective Studies in the General Population

Elevated circulating soluble CD30 (sCD30) has been previously associated with AIDS-related non-Hodgkin lymphoma (NHL) risk. This finding was recently extended to the general population where elevated levels of sCD30 were reported in prediagnostic serum among subjects that developed NHL later in life. We carried out a replication study within the Italian European Prospective Investigation into Cancer and Nutrition cohort. Plasma sCD30 concentration was measured by ELISA in prospectively collected blood of 35 B-cell lymphoma cases and 36 matched controls. We observed significantly increased relative risks for lymphoma with increasing sCD30 levels [OR (95% CI) for second and third tertiles vs. first tertile: 5.5 (1.5-20.2), 4.0 (1.1-13.9), respectively]. In addition, spline analyses showed that the dose-response curve of sCD30 and lymphoma risk was monotonic and quite similar to the risks reported in the previous study. This replication study adds to the evidence that sCD30 is related to future lymphoma risk in a concentration-dependent manner in the general population. The results of this study strengthen the observation that chronic sustained B-cell activation plays an important role in lymphomagenesis.

Age‐dependent changes of serum soluble CD30 concentration in children

CD30 was originally described as a marker on Reed-Sternberg cells in Hodgkin lymphoma. The extracellular portion of CD30 is proteolytically cleaved from CD30+ cells, to produce a soluble form of the molecule (sCD30) detectable in serum. Measurement of sCD30 concentration in serum has been suggested to be a potential tool in monitoring of inflammatory status in variety of diseases. Several investigators reported the relevance for sCD30 as a predictive marker for allograft rejection following organ transplantation. The aim of the study was to verify whether sCD30 serum concentrations may be affected by an age in healthy children. Heparinized venous blood was taken from 78 healthy children. For the analysis of sCD30 levels, the commercially available sCD30 ELISA was used. The sCD30 was detected in all serum samples and concentrations ranged from 6.75 to 68.07ng/mL. The statistical analysis of all individuals showed that sCD30 concentration was significantly age depended (r=-0.618, p<0.0001). When sCD30 concentrations were analyzed in regard to gender, no significant differences were identified in age subgroups.