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

Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1303-14. doi: 10.1158/1055-9965.EPI-11-0037. Epub 2011 Apr 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / blood
  • Acquired Immunodeficiency Syndrome / complications*
  • Acquired Immunodeficiency Syndrome / immunology
  • Adult
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / immunology
  • Case-Control Studies
  • Cytokines / blood*
  • Cytokines / immunology
  • Humans
  • 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
  • Middle Aged
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Cytokines

Grants and funding