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

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 20; no. 7; pp. 1303 - 1314
• Main Authors: Breen, Elizabeth Crabb, Hussain, Shehnaz K., Magpantay, Larry, Jacobson, Lisa P., Detels, Roger, Rabkin, Charles S., Kaslow, Richard A., Variakojis, Daina, Bream, Jay H., Rinaldo, Charles R., Ambinder, Richard F., Martinez-Maza, Otoniel
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.2011
• Subjects: Acquired Immunodeficiency Syndrome - blood; Acquired Immunodeficiency Syndrome - complications; Acquired Immunodeficiency Syndrome - immunology; Adult; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biological and medical sciences; Biomarkers, Tumor - blood; Biomarkers, Tumor - immunology; Case-Control Studies; Cytokines - blood; Cytokines - immunology; Human viral diseases; Humans; Infectious diseases; Lymphocyte Activation - immunology; Lymphoma, AIDS-Related - blood; Lymphoma, AIDS-Related - complications; Lymphoma, AIDS-Related - immunology; Lymphoma, B-Cell - blood; Lymphoma, B-Cell - complications; Lymphoma, B-Cell - immunology; Male; Medical sciences; Middle Aged; Tumors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Young Adult; Immunopathology; Immunostimulation; Cytokine; Biological marker; Biological indicator; AIDS; Malignant hemopathy; B-Lymphocyte; Systemic; Non Hodgkin lymphoma; Immune deficiency; Infection; Cancerology; Lymphoproliferative syndrome; Viral disease; β Cell; Diagnosis; Disseminated; Cancer
• ISSN: 1055-9965; 1538-7755; 1538-7755
• DOI: 10.1158/1055-9965.EPI-11-0037

Background: 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). Methods: 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. Results: 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. Conclusions: 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. Impact: 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. Cancer Epidemiol Biomarkers Prev; 20(7); 1303–14. ©2011 AACR.