Serum levels of the chemokine CXCL13, genetic variation in CXCL13 and its receptor CXCR5, and HIV-associated non-Hodgkin B-cell lymphoma risk

Shehnaz K. Hussain*, Weiming Zhu, Shen Chih Chang, Elizabeth Crabb Breen, Elena Vendrame, Larry Magpantay, Dan Widney, Daniel Conn, Mary Sehl, Lisa P. Jacobson, Jay H. Bream, Steven Wolinsky, Charles R. Rinaldo, Richard F. Ambinder, Roger Detels, Zuo Feng Zhang, Otoniel Martínez-Maza

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background: CXCL13 and CXCR5are a chemokine and receptor pair whose interaction is critical for naïve Bcell trafficking and activation within germinal centers. We sought to determine whether CXCL13 levels are elevated before HIV-associated non-Hodgkin B-cell lymphoma (AIDS-NHL), and whether polymorphisms in CXCL13 or CXCR5 are associated with AIDS-NHL risk and CXCL13 levels in a large cohort of HIV-infected men. Methods: CXCL13 levels were measured in sera from 179 AIDS-NHL cases and 179 controls at three timepoints. TagSNPs in CXCL13 (n = 16) and CXCR5 (n = 11) were genotyped in 183 AIDS-NHL cases and 533 controls. OR and 95% confidence intervals (CI) for the associations between one unit increase in log CXCL13 levels and AIDS-NHL, as well as tagSNP genotypes and AIDS-NHL, were computed using logistic regression. Mixed linear regression was used to estimate mean ratios (MR) for the association between tagSNPs and CXCL13 levels. Results: CXCL13 levels were elevated for more than 3 years (OR = 3.24;95% CI = 1.90-5.54), 1 to 3 years (OR=3.39;95% CI=1.94-5.94), and 0 to 1 year (OR=3.94;95% CI=1.98-7.81) before an AIDS-NHL diagnosis. The minor allele of CXCL13 rs355689 was associated with reduced AIDS-NHL risk (ORTCvsTT = 0.65;95% CI = 0.45-0.96) and reduced CXCL13 levels (MRCCvsTT = 0.82;95% CI = 0.68-0.99). The minor allele of CXCR5 rs630923 was associated with increased CXCL13 levels (MR AAvsTT = 2.40;95% CI = 1.43-4.50). Conclusions: CXCL13 levels were elevated preceding an AIDS-NHL diagnosis, genetic variation in CXCL13 may contribute to AIDS-NHL risk, and CXCL13 levels may be associated with genetic variation in CXCL13 and CXCR5. Impact: CXCL13 may serve as a biomarker for early AIDS-NHL detection.

Original languageEnglish (US)
Pages (from-to)295-307
Number of pages13
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number2
DOIs
StatePublished - Feb 2013

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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