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Serum Levels of the Chemokine CXCL13, Genetic Variation in CXCL13 and Its Receptor CXCR5, and HIV-Associated Non-Hodgkin B-Cell Lymphoma Risk

Year: 2012
Type: article
Study design: Observational Study
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. IMPACT: CXCL13 may serve as a biomarker for early AIDS-NHL detection.
DOI: 10.1158/1055-9965.epi-12-1122
Authors: 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
Institutions: Northwestern University, Johns Hopkins University, University of California, Los Angeles, University of Pittsburgh, Johns Hopkins Medicine, UCLA Jonsson Comprehensive Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: bronze
Funders: James B. Pendleton Charitable Trust, National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Research Resources
Awards: G1338448323, G1648982045, G2072110039, G2088232294, G2236897829, Institute for Clinical and Translational Research (UL1), Immune Dysfunction and AIDS-associated B Cell Lymphoma, G344188330, G3454032435, G359857122, Prediagnostic Markers of Immune Activation and Viral Infection and Risk of NHL, G414031072, Natural History of AIDS in Homosexual Men, G4348962262, G51363488, Center/Coordination, Analysis and Management/MACS, G536099884, Multicenter AIDS Cohort Study, G714446084, G758626889, UCLA Center for AIDS Research (CFAR), HIV-driven B cell activation: role in the genesis of AIDS-related lymphoma, Center for HIV Identification, Prevention and Treatment Services
OpenAlex ID: W2171159119
FWCI: 1.846
Cites: 62
Cited by: 57
Related to: 10