title: 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: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7076, USA. ebreen@mednet.ucla.edu
authors.forename: Elizabeth Crabb
authors.initials: EC
authors.lastname: Breen
authors.forename: Shehnaz K
authors.initials: SK
authors.lastname: Hussain
authors.forename: Larry
authors.initials: L
authors.lastname: Magpantay
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Charles S
authors.initials: CS
authors.lastname: Rabkin
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: Daina
authors.initials: D
authors.lastname: Variakojis
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martinez-Maza
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications* / Q000276:immunology; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016483:Lymphoma, AIDS-Related / Q000097:blood / Q000150:complications / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000097:blood / Q000150:complications / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines