B-Cell Stimulatory Cytokines and Markers of Immune Activation Are Elevated Several Years Prior to the Diagnosis of Systemic AIDS-Associated Non-Hodgkin B-Cell Lymphoma
ABSTRACT The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine whether elevated serum levels of molecules associated with B-cell activation precede the diagnosis of AIDS-associated NHL (AIDS-NHL).
Serum levels of B-cell activation-associated molecules, interleukin (IL)6, IL10, soluble CD23 (sCD23), sCD27, sCD30, C-reactive protein (CRP), and immunoglobulin E were determined in 179 NHL cases and HIV+ controls in the Multicenter AIDS Cohort Study, collected at up to 3 time points per subject, 0 to 5 years prior to AIDS-NHL diagnosis.
Serum IL6, IL10, CRP, sCD23, sCD27, and sCD30 levels were all significantly elevated in the AIDS-NHL group, when compared with HIV+ controls or with AIDS controls, after adjusting for CD4 T-cell number. Elevated serum levels of B-cell activation-associated molecules were seen to be associated with the development of systemic [non-CNS (central nervous system)] NHL, but not with the development of primary CNS lymphoma.
Levels of certain B-cell stimulatory cytokines and molecules associated with immune activation are elevated for several years preceding the diagnosis of systemic AIDS-NHL. This observation is consistent with the hypothesis that chronic B-cell activation contributes to the development of these hematologic malignancies.
Marked differences in serum levels of several molecules are seen for several years prediagnosis in those who eventually develop AIDS-NHL. Some of these molecules may serve as candidate biomarkers and provide valuable information to better define the etiology of NHL.
- SourceAvailable from: Brian Flepisi
- "B-cell activation is characterized by lymphocyte proliferation, class switch recombination (CSR), and somatic hypermutation, all of which are prone to resultant errors in DNA that may lead to lymphomagenesis. B-cell activation leads to the expression of activation induced cytidine deaminase (AICDA), a DNA modifying enzyme that mediates immunoglobulin gene CSR and somatic hypermutation.99 "
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- "Chronic B cell hyperactivation is driven by overproduction of B cell stimulatory cytokines, such as IL-6, IL-10, interferon-α (IFN-α), and tumor necrosis factor (TNF; Rieckmann et al., 1991; Takeshita et al., 1995; Mandl et al., 2008). The serum levels of these B cell stimulatory cytokines and other molecules, such as soluble sCD27 and sCD30 generated from the corresponding B cell receptors during the process of immune activation, were significantly high 1–5 years prior to diagnosis of systemic AIDS-NHL (Ambinder et al., 2010; Breen et al., 2011). Elevated serum levels of IL-6 have also been observed 1–3 years prior to the onset of AIDS-NHL, thus supporting the role of IL-6-driven B cell stimulation in the development of these lymphomas (Breen et al., 2011). "
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