Serum Levels of Cytokines and Biomarkers for Inflammation and Immune Activation, and HIV-Associated Non-Hodgkin B-Cell Lymphoma Risk

Abstract

Background: HIV infection is associated with a marked increase in risk for non-Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood. Methods: In this study serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1-to-5 years preceding AIDS-NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV+ controls from the Multicenter AIDS Cohort Study (MACS). Results: Multivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα were elevated in those HIV+ individuals who went on to develop AIDS-NHL. Additionally, the fraction of specimens with detectable IL-2 was increased, and the fraction with detectable IL-4 was decreased, in these subjects. Conclusions: These results suggest that long term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV+ individuals. Impact: FLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα may serve as biomarkers for AIDS-NHL.

A cross-sectional study of C-type lectin receptors (CD94 and CD314) in patients with HIV/AIDS and cancer

“…As previously mentioned, neoplastic conditions contemplated in our HIV/AIDSWC study group can induce the production of such inflammatory cytokines [40][41]. However, despite the increase in CD94 receptor expression of patients HIV/AIDSWC to compare them with HIV/AIDS group, this was not statistically significant, and compare them with healthy donors except for inconclusive expression CD56bright in percentages also there were no significant differences.…”

“…The various cancers and oncovirus associated with HIV-1 (which make up much of the tumor manifestations found in our group with HIV/AIDSWC) are capable of overactive such inflammatory responses by the secretion of these pro-inflammatory cytokines, chemotaxis and the extravasation of lymphocytes the site of infection [40][41] The present study was unable to establish a stratified subpopulations of CD4+ and CD8+, due to the lack of suitable markers. Porting is not possible to identify whether the increase in this population NKG2D+ is due in fact to the CD4+ or CD8+ lymphocytes that would be increased in view of the conditions of infection, immunodeficiency and cancer.…”

Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

“…Though the mechanisms underlying HIV-associated B-cell activation are largely undefined, we demonstrated that Toll-like receptor ligands (TLR-L), resulting from HIV infection associated elevated microbial translocation [8,9], likely contributes to B-cell hyperactivation [10]. Additionally, prior work demonstrated that HIV infection is associated with elevated levels of several B cell stimulatory molecules, with increasingly heightened levels observed preceding AIDS-NHL diagnosis [6,7,11,12].…”

A lymphomagenic role for HIV beyond immune suppression?

“…The underlying chronic antigenic stimulation and inflammation may lead to a polyor oligo-clonal expansion of dysregulated B lymphocytes, which is also favored by the abnormal production of B-cell growthpromoting cytokines such as IL-6 and IL-10. 41 Uncontrolled persistent stimulation of B lymphocytes may favor the emergence of monoclonal B-cell proliferations that are at increased risk of acquiring critical genetic alterations, ultimately leading to lymphoma development. Notably, CD40 ligand (CD40L), a costimulatory molecule expressed by activated T lymphocytes, can be inserted at the surface of HIV-1 particles when budding from activated CD4…”