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

Hosnijeh, Fatemeh Saberi; Kolijn, P. Martijn; Casabonne, Delphine; Nieters, Alexandra; Solans, Marta; Naudin, Sabine; Ferrari, Pietro; McKay, James; Weiderpass, Elisabete; Perduca, Vittorio; Besson, Caroline; Mancini, Francesca Romana; Masala, Giovanna; Ricceri, Fulvio; Huerta, José María; Petrova, Dafina; Sala, Núria; Trichopoulou, Antonia; Karakatsani, Anna; Vecchia, Carlo La; Kaaks, Rudolf; Canzian, Federico; Aune, Dagfinn; Boeing, Heiner; Schulze, Matthias B.; Pérez-Cornago, Aurora; Langerak, Anton W.; Velden, Vincent H.J. van der; Vermeulen, Roel

doi:10.1038/s41598-020-70790-9

Cited by 4 publications

(4 citation statements)

References 47 publications

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“…In this context, the association of CXCL13 serum levels in pSS patients with clinical and laboratory markers of B cell activation, including rheumatoid factor, hypergammaglobulinemia, hypocomplementemia, and high disease activity was rather anticipated. Furthermore, elevated CXCL13 levels have been linked to prediction, presence, prognosis and/or therapeutic response of NHLs (47)(48)(49)(50)(51). Although our findings along with previous studies (27,29), indicate that CXCL13 serum levels in pSS patients may associate with high risk to develop NHL, all studies failed to register CXCL13 serum levels as an independent lymphoma predictor.…”

Section: Discussioncontrasting

confidence: 51%

Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Minor Salivary Gland Lesions and Other Histologic Parameters in Patients With Sjögren’s Syndrome

et al. 2021

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Recent studies suggest that elevated CXCL13 serum levels in patients with primary Sjögren’s syndrome (pSS) associate with minor salivary gland (MSG) histologic features, disease severity, as well as high-risk status for non-Hodgkin lymphoma (NHL) development and NHL itself. In contrast, limited discriminative value of CXCL13 saliva levels has been reported. Prompt by these reports, we sought to validate the clinical utility of CXCL13 by investigating potential correlations of serum and saliva levels with MSG histopathologic [including CXCL13+-cell number, severity of infiltrates and germinal center (GC) formation], serologic and clinical parameters, as well as NHL. CXCL13 levels were evaluated in paired serum and saliva specimens of 45 pSS patients (15 with NHL; pSS-associated NHL: SSL), 11 sicca-controls (sicca-complaining individuals with negative MSG biopsy and negative autoantibody profile), 10 healthy individuals (healthy-controls) and 6 non-SS-NHLs. CXCL13+-cells were measured in paired MSG-tissues of 22 of pSS patients studied (including 7 SSLs) and all sicca-controls. CXCL13 serum levels were significantly increased in pSS and SSL patients compared to sicca- and healthy-controls and were positively correlated with the CXCL13+-cell number and biopsy focus-score. Serum CXCL13 was significantly higher in pSS patients with GCs, rheumatoid factor, hypocomplementemia, high disease activity, NHL and in high-risk patients for NHL development. CXCL13 saliva levels were significantly increased in SSL patients (compared to non-SS-NHLs), patients with GCs and in high-risk for NHL patients. Univariate analysis revealed that CXCL13 serum, but not saliva, levels were associated with lymphoma, an association that did not survive multivariate analysis. Conclusively, our findings confirm that serum, but not saliva, levels of CXCL13 are associated with histologic, serologic and clinical features indicative of more severe pSS.

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Section: Discussioncontrasting

confidence: 51%

Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Minor Salivary Gland Lesions and Other Histologic Parameters in Patients With Sjögren’s Syndrome

et al. 2021

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“…sCD27, sCD30 and CXCL13 were moderately correlated with one another among controls within each cohort, with Spearman correlation coefficients ranging from 0.27 to 0.51 (Table S3), which is similar to previous studies. 32,33 In the two studies that measured all three markers (ATBC and WHI), sCD27 and sCD30 levels were more strongly correlated with one another than with CXCL13 levels.…”

Section: Resultsmentioning

confidence: 96%

Circulating immune markers and risks of non‐Hodgkin lymphoma subtypes: A pooled analysis

Rhee

Birmann

Roos

et al. 2022

Intl Journal of Cancer

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Although prediagnostic circulating concentrations of the immune activation markers soluble CD27 (sCD27), sCD30 and chemokine ligand‐13 (CXCL13) have been associated with non‐Hodgkin lymphoma (NHL) risk, studies have been limited by sample size in associations with NHL subtypes. We pooled data from eight nested case‐control studies to investigate subtype‐specific relationships for these analytes. Using polytomous regression, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) relating study‐specific analyte tertiles to selected subtypes vs controls (n = 3310): chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n = 623), diffuse large B cell lymphoma (DLBCL; n = 621), follicular lymphoma (FL; n = 398), marginal zone lymphoma (MZL; n = 138), mantle cell lymphoma (MCL; n = 82) and T cell lymphoma (TCL; n = 92). We observed associations with DLBCL for elevated sCD27 [OR for third vs first tertile (ORT3) = 2.2, 95% CI = 1.6‐3.1], sCD30 (ORT3 = 2.0, 95% CI = 1.6‐2.5) and CXCL13 (ORT3 = 2.3, 95% CI = 1.8‐3.0). We also observed associations with sCD27 for CLL/SLL (ORT3 = 3.3, 95% CI = 2.4‐4.6), MZL (ORT3 = 7.7, 95% CI = 3.0‐20.1) and TCL (ORT3 = 3.4, 95% CI = 1.5‐7.7), and between sCD30 and FL (ORT3 = 2.7, 95% CI = 2.0‐3.5). In analyses stratified by time from phlebotomy to case diagnosis, the sCD27‐TCL and all three DLBCL associations were equivalent across both follow‐up periods (<7.5, ≥7.5 years). For other analyte‐subtype comparisons, associations were stronger for the follow‐up period closer to phlebotomy, particularly for indolent subtypes. In conclusion, we found robust evidence of an association between these immune markers and DLBCL, consistent with hypotheses that mechanisms related to immune activation are important in its pathogenesis. Our other findings, particularly for the rarer subtypes MZL and TCL, require further investigation.

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“…In a nested case‐control study some markers of sustained B‐ cell activation were predictive of B‐cell lymphoma risk, namely sCD23, sCD27, sCD30, and CXCL13. Also, sCD23 and CXCL13 partly mediated the causal pathway association between positive Body Mass Index (BMI) and Diffuse Large B‐Cell Lymphoma (DLBCL) risk 29 . Associations have also been reported between increased risk of NHL and polymorphisms in obesity‐related genes such as leptin (LEP) and leptin receptor, 2,3 key regulators of energy balance and immune function.…”

Section: Reviewmentioning

confidence: 99%

“…Also, sCD23 and CXCL13 partly mediated the causal pathway association between positive Body Mass Index (BMI) and Diffuse Large B-Cell Lymphoma (DLBCL) risk. 29 Associations have also been reported between increased risk of NHL and polymorphisms in obesity-related genes such as leptin (LEP) and leptin receptor, 2,3 key regulators of energy balance and immune function. Indeed, polymorphisms in the LEP gene (2548G>A, 19A>G), associated with high circulating leptin levels, were identified as susceptibility loci for NHL in two independent studies.…”

Section: Biological Correlations Between Nutritional Status and Lymphomamentioning

confidence: 99%

Host‐related factors and cancer: Malnutrition and non‐Hodgkin lymphoma

Mancuso

Mattana

Santoro

et al. 2022

Hematological Oncology

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Assessment of host‐related factors is a crucial aspect in the comprehensive management of cancer patients. A distinct nutritional disturbance linked to cancer has been recognized to be associated with negative outcomes. However, compared to solid tumors, only a limited number of studies have looked specifically at nutritional issues in the field of lymphoma. The aim of this review is to integrate the current knowledge on interactions between malnutrition and lymphoma and address most relevant and pertinent questions. We first provide a literature review on the mutual biological relationship between malnutrition and lymphoma. Next, we explore the overlap between malnutrition, sarcopenia, cachexia and frailty in lymphoma studies. In addition, we summarize the clinical assessment scales used to measure malnutrition in lymphoma subjects. Furthermore, we address the problem of nutritional interventions aimed at patients who are candidates for treatment for lymphoma. Malnutrition can arise as a consequence of lymphoma disease and can in turn promote lymphomagenesis, negatively affect the response to therapy and favor adverse event to treatment. There is increasing evidence that malnutrition, sarcopenia and cachexia in lymphoma are intimately inter‐related and are a hallmark of frailty. A variety of different tools are recorded with the apparent ability to describe nutritional status and to impact prognosis in lymphoma patients. Finally, a network of prognostic host‐ and disease‐related factors is proposed where malnutrition can interact with each other in complex ways.

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

Cited by 4 publications

References 47 publications

Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Minor Salivary Gland Lesions and Other Histologic Parameters in Patients With Sjögren’s Syndrome

Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Minor Salivary Gland Lesions and Other Histologic Parameters in Patients With Sjögren’s Syndrome

Circulating immune markers and risks of non‐Hodgkin lymphoma subtypes: A pooled analysis

Host‐related factors and cancer: Malnutrition and non‐Hodgkin lymphoma

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