Elena Vendrame1, Shehnaz K Hussain, Elizabeth Crabb Breen, Larry I Magpantay, Daniel P Widney, Lisa P Jacobson, Daina Variakojis, Emilee R Knowlton, Jay H Bream, Richard F Ambinder, Roger Detels, Otoniel Martínez-Maza. 1. Authors' Affiliations: University of California Los Angeles (UCLA) AIDS Institute, Jonsson Comprehensive Cancer Center at UCLA, Departments of Obstetrics and Gynecology, Psychiatry and Biobehavioral Sciences, and Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Department of Epidemiology, UCLA School of Public Health, Los Angeles, California; Departments of Epidemiology and Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health and Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
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), interleukin (IL)-6, IL-10, IP-10/CXCL10, neopterin, and TNF-α were elevated in those HIV(+) individuals who went on to develop AIDS-NHL. In addition, 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 TNF-α may serve as biomarkers for AIDS-NHL. .
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), interleukin (IL)-6, IL-10, IP-10/CXCL10, neopterin, and TNF-α were elevated in those HIV(+) individuals who went on to develop AIDS-NHL. In addition, 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 TNF-α may serve as biomarkers for AIDS-NHL. .
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