First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
Hospital of University of International Business and Economics, Beijing, China.
Front Immunol. 2024 Sep 25;15:1431261. doi: 10.3389/fimmu.2024.1431261. eCollection 2024.
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% 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.
最近的研究证实，代谢物和免疫细胞表型可能与淋巴瘤的风险相关。然而，代谢物、免疫细胞表型、疾病风险之间的双向因果关系，以及免疫是否是代谢物与淋巴瘤因果关系之间的中介，仍不清楚。
为了阐明代谢物、免疫细胞表型与淋巴瘤之间的因果关系，我们使用了两样本 Mendelian 随机化（MR）和两步 MR 分析。
应用大规模全基因组关联研究（GWAS）汇总数据，我们选择了 1400 种代谢物和 731 种免疫细胞表型，用于八种淋巴瘤亚型的两样本双向 MR 分析。此外，我们使用两步 MR 来量化免疫细胞表型对淋巴瘤中代谢物作用的比例。
本研究发现 17 种代谢物与淋巴瘤之间存在双向因果关系，12 种免疫细胞表型与淋巴瘤之间也存在双向因果关系。此外，我们发现代谢物与淋巴瘤之间存在因果关系，其中三组是由免疫细胞表型介导的。其中，浆母细胞/浆细胞（PB/PC）上的 CD27 是精氨酸对谷氨酸比率与慢性淋巴细胞白血病正相关的一个介导物，其介导比例为 14.60%（95%CI=1.29-28.00%，P=3.17×10-2）。所有淋巴细胞中自然杀伤（NK）细胞的百分比（NK%lymphocyte）是 X-18922（未知代谢物）水平与弥漫性大 B 细胞淋巴瘤之间负相关的一个介导物，其介导比例为-8.940%（95%CI=-0.063-(-17.800) %，P=4.84×10-2）。IgD-CD24-B 细胞上的 CD25 是 X-24531（未知代谢物）水平与弥漫性大 B 细胞淋巴瘤之间正相关的一个介导物，其介导比例为 13.200%（95%CI=-0.156-26.200%，P=4.73×10-2）。
在本研究中，我们确定了代谢物与淋巴瘤之间的因果关系，其中免疫细胞表型作为介导物仅涉及一小部分。大多数代谢物影响淋巴瘤发展风险的介导物仍不清楚，需要在未来进一步探索。
