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Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development.

ABSTRACT: Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled?>?9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve?=?0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.

SUBMITTER: Saberi Hosnijeh F

PROVIDER: S-EPMC7429856 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development.

Saberi Hosnijeh Fatemeh F Kolijn Pieter M PM Casabonne Delphine D Nieters Alexandra A Solans Marta M Naudin Sabine S Ferrari Pietro P Mckay James D JD Weiderpass Elisabete E Perduca Vittorio V Besson Caroline C Mancini Francesca Romana FR Masala Giovanna G Krogh Vittorio V Ricceri Fulvio F Huerta José M JM Petrova Dafina D Sala Núria N Trichopoulou Antonia A Karakatsani Anna A La Vecchia Carlo C Kaaks Rudolf R Canzian Federico F Aune Dagfinn D Boeing Heiner H Schulze Matthias B MB Perez-Cornago Aurora A Langerak Anton W AW van der Velden Vincent H J VHJ Vermeulen Roel R

Scientific reports 20200814 1

Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 i ...[more]

PMID: 32796953

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Project description:IMPORTANCE:Dyslipidemia in young adults in the United States during their childbearing years is common, and the consequences for the next generation are poorly understood. Further understanding of the harmful consequences of elevated low-density lipoprotein cholesterol (LDL-C) levels in young adults may help to inform population screening and management strategies. OBJECTIVE:To examine whether adult levels of serum LDL-C are associated with maternal prepregnancy LDL-C levels beyond that attributable to inherited genetic sequence polymorphisms, diet, physical activity, and body mass index. DESIGN, SETTING, AND PARTICIPANTS:The Framingham Heart Study is a multigenerational, population-based inception cohort initiated in 1948 in Framingham, Massachusetts. In this study of families, the analyses included 538 parent-offspring pairs with parental LDL-C levels measured in the study prior to the offspring's birth. Parental prebirth, parental concurrent, and adult offspring assessments occurred in 1971-1983, 1998-2001, and 2002-2005, respectively. Data analyses were conducted between March 1, 2013, and May 30, 2015. EXPOSURES:Maternal prepregnancy LDL-C levels compared with paternal prepregnancy and parental concurrent LDL-C levels in association with adult offspring LDL-C levels. MAIN OUTCOMES AND MEASURES:Adult offspring LDL-C levels were examined as both a continuous and dichotomous outcome (using a threshold of 130 mg/dL). RESULTS:Among the 538 parent-offspring pairs, there were 241 mother-offspring and 297 father-offspring pairs with a mean (SD) offspring age of 26 (3) years. Adult offspring LDL-C levels were associated with maternal prepregnancy LDL-C levels after adjustment for family relatedness and offspring lifestyle, anthropometric factors, and inherited genetic variants (??=?0.32 [SE, 0.05] mg/dL; P?<?.001). After multivariable adjustment, adults who had been exposed to elevated maternal prepregnancy LDL-C levels were at a 3.8 (95% CI, 1.5-9.8) times higher odds of having elevated LDL-C levels (P?=?.005) and had an adjusted LDL-C level of 18 mg/dL (95% CI, 9-27 mg/dL) higher than did those without such exposure. Maternal prepregnancy LDL-C levels explained 13% of the variation in adult offspring LDL-C levels beyond common genetic variants and classic risk factors for elevated LDL-C levels. CONCLUSIONS AND RELEVANCE:Adult offspring dyslipidemia is associated with maternal prepregnancy dyslipidemia in excess of measured lifestyle, anthropometric, and inherited genetic factors. The findings support the possibility of a maternal epigenetic contribution to cardiovascular disease risk in the general population. Further research is warranted to determine whether ongoing public health efforts to identify and reduce dyslipidemia in young adults prior to their childbearing years may have additional potential health benefits for the subsequent generation.

Project description:BackgroundTreated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that anisocytosis, as measured by red cell distribution width (RDW), is independently associated with prevalent CVD in people living with HIV (PLHIV). In this study, we sought to identify immune correlates of RDW in PLHIV receiving antiretroviral therapy.MethodsWe performed a cross-sectional and longitudinal analysis of 147 virally-suppressed PLHIV, who had LDL < 130 mg/dL and evidence of heightened inflammation, in a randomized trial of statin therapy. A complete blood count and biomarkers of inflammation and immune activation/exhaustion were measured in peripheral blood at entry and after 24 and 48 weeks. Associations with RDW were estimated using linear regression and linear mixed models.ResultsThe median age (IQR) for the cohort at enrollment was 46 (40-53) years; 78% were male and 68% were African American. The median RDW for the cohort was 13.4% (12.9-14.0). Compared with the lowest RDW tertile, patients in the highest tertile were less likely to be male, and more likely to be African American, have lower hemoglobin, lower mean corpuscular volume, and higher platelet counts (all P < 0.05). At baseline, RDW weakly correlated with C-reactive protein (r = 0.196), d-dimer (r = 0.214), fibrinogen (r = 0.192), IL-6 (r = 0.257), CD4+DR+38+ T cells (r = 0.195), and CD4+PD1+ T cells (r = 0.227), all P < 0.05. Only IL-6, CD4+38+DR+ T cells, and CD4+PD1+ T_cells remained associated after adjustment for clinical factors known to affect RDW in the general population. Over 48 weeks, RDW did not change and there was no significant effect of statin (P = 0.45). After adjustment for clinical parameters, RDW remained positively associated with CD4+38+DR+ and CD4+PD1+ T cells across all time points (P = 0.05).ConclusionIn this population of treated HIV+ subjects, anisocytosis was associated with biomarkers of inflammation and T-cell activation/exhaustion over time and independent of clinical confounders. Therefore, RDW may be a useful prognostic biomarker of cardiovascular risk that partially reflects chronic inflammation and immune exhaustion in PLHIV receiving antiretroviral therapy.

Dataset Information

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development.

Publications

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development.

Similar Datasets

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