Elevated serum soluble CD30 precedes the development of AIDS-associated non-Hodgkin's B cell lymphoma.
ABSTRACT CD30, first described as the Ki antigen on malignant B cells in Hodgkin's lymphoma, is also expressed on normal activated B and T cells. It can be cleaved from the cell surface and detected in normal serum as soluble CD30 (sCD30), where it can be an indicator of levels of immune activation. In a cross-sectional study utilizing archived sera at a time point close to but preceding a diagnosis of acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's B cell lymphoma, AIDS lymphoma subjects (n = 49) showed elevated mean levels of sCD30 compared to controls with AIDS but no malignancy (n = 44, p < 0.01), HIV-infected but relatively healthy (n = 47, p < 0.001), or HIV-seronegative controls (n = 44, p < 0.001). Serum sCD30 was significantly correlated to serum levels of the B cell cytokines interleukin-6 (IL-6), IL-10, and sCD23, but only among lymphoma subjects (p < or = 0.05). Correlations between sCD30 and other markers of immune system activation were seen among all HIV-infected subjects (sCD27, sCD44, CXCL13, p < 0.05). These observations suggest that sCD30, especially in combination with other immune system molecules, could be an important biomarker for an immune system environment conducive to B cell hyperactivation and the development of AIDS-associated B cell lymphoma.
- SourceAvailable from: Shigeki Takemoto[Show abstract] [Hide abstract]
ABSTRACT: Human T-cell leukemia virus type 1 infection makes CD4+ T cells transformed into leukemic cells, whereas human immunodeficiency virus make them destroyed. Interestingly, activation of CD30 led to the induction of apoptotic death of anaplastic large cell lymphoma cells, while Hodgkin's lymphoma cells, which constitutively express NF-κB, were not susceptible to CD30-induced apoptosis. Such a pleiotropic effect of CD30 signaling is dependent on cell type, B-cell or T-cell, and probably different activation status of NF-κB, constitutive or inducible.Accordingly, CD30 triggering may be responsible for the enhanced retroviral replication and T cell death under the influence of T cell activation and/or NF-κB activation status, showing high levels of sCD30.
- [Show abstract] [Hide abstract]
ABSTRACT: The CD30L ligand is a membrane-associated glycoprotein expressed by activated CD4(+)Th cells, macrophages, dendritic cells, and B lymphocytes. It binds to the CD30 receptor carried on activated and helper Th cells, inducing the immune response and apoptosis. The aim of this retrospective study was to determine the level of sCD30L in the serum of patients at diagnosis of ovarian cancer and at relapse and to assess the potential association of this ligand with selected clinico-pathologic factors. We studied 69 patients with ovarian cancer allocated to two groups: A - ovarian cancer at diagnosis, B - relapse of ovarian cancer and active growth of the tumor. We found high levels of sCD30L in ovarian cancer patients. Levels at relapse (21.48 ng/ml) were significantly higher than at diagnosis (11.81 ng/ml). Poor response to first-line chemotherapy was accompanied by higher levels of sCD30L and by several other findings: resistance to platinum analogs was common, neoadjuvant chemotherapy was needed, relapse and death during two-year follow-up were frequent. Our present study might initially suggest that elevated concentration of sCD30L can be an important finding prognosticating a poor prognosis and is associated with platinum resistant and refractory cases of ovarian cancer. However, studies are needed on larger groups of patients.Contemporary Oncology / Wspólczesna Onkologia 01/2012; 16(6):520-525. DOI:10.5114/wo.2012.32485 · 0.22 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: A nested case-control study was performed within the Italian cohort of naïve to antiretroviral human immunodeficiency virus (HIV) patients (ICONA) cohort to evaluate the role of serum free light chains (sFLC) in predicting non-Hodgkin's lymphoma (NHL) and Hodgkin lymphoma (HL) in HIV-infected individuals. Of 6513 participants, 86 patients developed lymphoma and 46 of these (NHL, 30; HL, 16) were included in this analysis having stored prediagnostic blood. A total of 46 serum case samples matched 1:1 to lymphoma-free serum control samples were assayed for κ and λ sFLC levels and compared by using conditional logistic regression. Because the polyclonal nature of free light chains (FLCs) was the focus of our study, we introduced the k + λ sum as the measurement of choice and as the primary variable studied. κ + λ sFLC values were significantly higher in patient with lymphoma than in controls, especially when considering samples stored 0-2-year period before the lymphoma diagnosis. In the multivariable analysis, the elevation of sFLC predicted the risk of lymphoma independently of CD4 count, (odd ratio of 16.85 for k + λ sFLC >2-fold upper normal limit (UNL) vs. normal value). A significant reduction in the risk of lymphoma (odd ratio of 0.07 in model with k + λ sFLC) was found in people with low sFLC and undetectable HIV viremia lasting more than 6 months. Our analysis indicates that an elevated polyclonal sFLC is a strong and sensitive predictor of the risk of developing lymphomas, and it is an easy to measure biomarker that merits consideration for introduction in routine clinical practice in people with HIV.American Journal of Hematology 08/2012; 87(8):749-53. DOI:10.1002/ajh.23236 · 3.48 Impact Factor