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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1431261
This article is part of the Research Topic Novel Approaches for Immunotherapy of Lymphoma View all 6 articles
Metabolite, immunocyte phenotype, and lymphoma: a Mendelian randomization Study
Provisionally accepted- 1 First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
- 2 National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, tianjing, China
- 3 University Hospital of International Business and Economics, Beijing, China
Recent studies have confirmed that metabolites and immunocyte phenotype may be associated with the risk of lymphoma. However, the bidirectional causality between metabolites, immunocyte phenotype, disease risk, and whether immunity is an intermediate mediator between metabolism and lymphoma causality is still unclear.To elucidate the causal relationship between metabolites, immune cell phenotypes, and lymphomas, we used two-sample Mendelian randomization (MR) and two-step MR analysis.Applying large-scale genome-wide association studies (GWAS) pooled data, we selected 1400 metabolites and 731 immunocyte phenotypes with eight lymphoma subtypes for two-sample bi-directional MR analysis. In addition, we used two-step MR to quantify the proportion of metabolite effects on lymphomas mediated by immunocyte phenotype.This study yielded a bidirectional causal relationship between 17 metabolites and lymphoma and a bidirectional causal relationship between 12 immunocyte phenotypes and lymphoma.In addition, we found causal associations between metabolites and lymphomas, three groups of which were mediated by immunocyte phenotypes. Among them, CD27 on plasmablast/plasma cell (PB/PC) was a mediator of the positive association of arginine to glutamate ratio with chronic lymphocytic leukemia, with a mediator ratio of 14.60% (95% 3 CI=1.29-28.00%, P=3.17 × 10-2). Natural killer (NK) cells as a percentage of all lymphocytes(NK %lymphocyte) was a mediator of the negative association of X-18922 ( unknown metabolite ) levels with diffuse large B-cell lymphoma, with a mediation proportion of -8.940% (95% CI=-0.063-(-17.800) %, P=4.84 × 10-2). CD25 on IgD-CD24-B cell was the mediator of the positive association between X-24531 ( unknown metabolite ) levels and diffuse large B-cell lymphoma, with a mediation proportion of 13.200% (95% CI=-0.156-26.200%, P=4.73 × 10-2).In the present study, we identified a causal relationship between metabolites and lymphoma, in which immunocyte phenotypes as mediators are involved in only a minor part. The mediators by which most metabolites affect the risk of lymphoma development remain unclear and require further exploration in the future.
Keywords: immunocyte phenotype, Mendelian randomization, Lymphoma, metabolite, intermediation factor
Received: 11 May 2024; Accepted: 09 Sep 2024.
Copyright: © 2024 Fan, Yuan, Yang, Zhang, Wang, Xie, He, Chen, Yan and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Pengying Yuan, University Hospital of International Business and Economics, Beijing, China
Xiangdong Yang, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
Weifeng Zhang, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
Xingli Wang, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
Juan Xie, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
Jing He, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
Haijing Chen, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
Lixiang Yan, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
Zhexin Shi, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
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