title: Serum levels of the chemokine CXCL13, genetic variation in CXCL13 and its receptor CXCR5, and HIV-associated non-hodgkin B-cell lymphoma risk.
abstract: BACKGROUND
  CXCL13 and CXCR5 are a chemokine and receptor pair whose interaction is critical for naïve B-cell 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 time-points. 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 (OR(TCvsTT) = 0.65; 95% CI = 0.45-0.96) and reduced CXCL13 levels (MR(CCvsTT) = 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.
  
  
  CONCLUSIONS
  CXCL13 may serve as a biomarker for early AIDS-NHL detection.
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA. skhussain@ucla.edu
authors.forename: Shehnaz K
authors.initials: SK
authors.lastname: Hussain
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhu
authors.forename: Shen-Chih
authors.initials: SC
authors.lastname: Chang
authors.forename: Elizabeth Crabb
authors.initials: EC
authors.lastname: Breen
authors.forename: Elena
authors.initials: E
authors.lastname: Vendrame
authors.forename: Larry
authors.initials: L
authors.lastname: Magpantay
authors.forename: Dan
authors.initials: D
authors.lastname: Widney
authors.forename: Daniel
authors.initials: D
authors.lastname: Conn
authors.forename: Mary
authors.initials: M
authors.lastname: Sehl
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
authors.forename: Steven
authors.initials: S
authors.lastname: Wolinsky
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D054382:Chemokine CXCL13 / Q000097:blood* / Q000235:genetics*; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D016393:Lymphoma, B-Cell / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D054380:Receptors, CXCR5 / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D054382:Chemokine CXCL13; D054380:Receptors, CXCR5