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.
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ABSTRACT: Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods: This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed bead-based immunoassays. Results: A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions: These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease.PLoS ONE 06/2014; 9(6):e99144. DOI:10.1371/journal.pone.0099144 · 3.53 Impact Factor
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ABSTRACT: Increasing evidence indicates that a dysregulated immune system, as the one found in allergic disorders, can affect survival of tumor cells. A possible association between allergies and risk of hematologic malignancies has been examined in several epidemiological studies, however, results were not always consistent. The aim of this review is to report the preclinical and clinical data, which support a correlation between allergy and hematologic neoplasms. Immune system modulation could represent a powerful tool in the prevention and treatment of hematologic malignancies.Leukemia Research 10/2014; 38(10). DOI:10.1016/j.leukres.2014.08.004 · 2.69 Impact Factor