title: Circulating mediators of inflammation and immune activation in AIDS-related non-hodgkin lymphoma.
abstract: BACKGROUND
  Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation.
  
  
  METHODS
  This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed bead-based immunoassays.
  
  
  RESULTS
  A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers.
  
  
  CONCLUSIONS
  These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease.
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Nolen
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America; UCLA AIDS Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Elizabeth Crabb
authors.initials: EC
authors.lastname: Breen
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Jenkins
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Kingsley
authors.affiliation: Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Ob/Gyn, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Lokshin
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor