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

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 (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. Impact: CXCL13 may serve as a biomarker for early AIDS-NHL detection.