Dataset Information

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

ABSTRACT: 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.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.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).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.CXCL13 may serve as a biomarker for early AIDS-NHL detection.

SUBMITTER: Hussain SK

PROVIDER: S-EPMC3703445 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Hussain Shehnaz K SK Zhu Weiming W Chang Shen-Chih SC Breen Elizabeth Crabb EC Vendrame Elena E Magpantay Larry L Widney Dan D Conn Daniel D Sehl Mary M Jacobson Lisa P LP Bream Jay H JH Wolinsky Steven S Rinaldo Charles R CR Ambinder Richard F RF Detels Roger R Zhang Zuo-Feng ZF Martínez-Maza Otoniel O

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20121218 2

<h4>Background</h4>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.<h4>Methods</h4>CXCL13 levels were measured in sera from 179 AIDS-NHL cases ...[more]

PMID: 23250934

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Project description:BackgroundC-X-C chemokine ligand 13 (CXCL13) is frequently elevated in cerebrospinal fluid (CSF) in a variety of inflammatory central nervous system (CNS) diseases, has been detected in meningeal B cell aggregates in brain tissues of multiple sclerosis patients, and proposedly recruits B cells into the inflamed CNS. Besides B cells also follicular helper T (Tfh) cells express the cognate receptor C-X-C chemokine receptor type 5 (CXCR5) and follow CXCL13 gradients in lymphoid tissues. These highly specialized B cell helper T cells are indispensable for B cell responses to infection and vaccination and involved in autoimmune diseases. Phenotypically and functionally related circulating CXCR5+CD4 T cells occur in blood. Their co-recruitment to the inflamed CSF is feasible but unresolved.MethodsWe approached this question with a retrospective study including data of all patients between 2017 and 2019 of whom immune phenotyping data of CXCR5 expression and CSF CXCL13 concentrations were available. Discharge diagnoses and CSF laboratory parameters were retrieved from records. Patients were categorized as pyogenic/aseptic meningoencephalitis (ME, n = 29), neuroimmunological diseases (NIMM, n = 22), and non-inflammatory neurological diseases (NIND, n = 6). ANOVA models and Spearman's Rank-Order correlation were used for group comparisons and associations of CXCL13 levels with immune phenotyping data.ResultsIn fact, intrathecal CXCL13 elevations strongly correlated with CXCR5+CD4 T cell frequencies in the total cohort (p < 0.0001, r = 0.59), and ME (p = 0.003, r = 0.54) and NIMM (p = 0.043, r = 0.44) patients. Moreover, the ratio of CSF-to-peripheral blood (CSF/PB) frequencies of CXCR5+CD4 T cells strongly correlated with CXCL13 levels both in the total cohort (p = 0.001, r = 0.45) and ME subgroup (p = 0.005, r = 0.50), indicating selective accumulation. ME, NIMM and NIND groups differed with regard to CSF cell counts, albumin quotient, intrathecal IgG, CXCL13 elevations and CXCR5+CD4 T cells, which were higher in inflammatory subgroups.ConclusionThe observed link between intrathecal CXCL13 elevations and CXCR5+CD4 T cell frequencies does not prove but suggests recruitment of possible professional B cell helpers to the inflamed CSF. This highlights CSF CXCR5+CD4 T cells a key target and potential missing link to the poorly understood phenomenon of intrathecal B cell and antibody responses with relevance for infection control, chronic inflammation and CNS autoimmunity.

Dataset Information

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

Publications

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

Similar Datasets

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