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循环的炎症性细胞因子和扩散的大B细胞淋巴瘤之间的因果关系:双向的门德尔随机化研究

Jieni Yu¹, Leihua Fu¹, Zhijian Zhang¹

¹Department of Hematology, Shaoxing People's Hospital, Shaoxing, Zhejiang, People's Republic of China.

Clinical and experimental medicine

|November 1, 2023

概括

这项研究揭示了因干扰素玛 (MIG/CXCL9) 和干扰素玛诱导蛋白10 (IP-10/CXCL10) 诱导的高水平的Monokine可能会因果性地增加扩散大B细胞淋巴瘤 (DLBCL) 的风险. 反过来,DLBCL似乎会提升巨细胞殖民地刺激因子 (M-CSF),瘤亡因子β (TNF-β) 和与TNF相关的诱导亡的配体 (TRAIL).

科学领域:

免疫学和瘤学
遗传流行病学遗传流行病学

背景情况:

扩散性大B细胞淋巴瘤 (DLBCL) 是非霍奇金淋巴瘤最常见的形式.
炎症性细胞因子涉及DLBCL的发病,但因果关系被反循环所掩盖.

研究的目的:

使用双向门德尔随机化方法研究DLBCL和特定的炎症性细胞因子之间的潜在因果关系.
为了确定DLBCL的上游炎症驱动因素和DLBCL对细胞因子水平的下游影响.

主要方法:

一个双向的门德尔随机化研究,利用来自全基因组关联研究的遗传变异.
来自8293名欧洲参与者的细胞因子相关遗传变异和1010例DLBCL病例的数据来自FinnGen联盟.
主要分析采用逆变量加权 (IVW) 方法,并补充了MR-Egger,加权中位数和MR-PRESSO灵敏度分析.

主要成果:

由干扰素马 (MIG/CXCL9) 和干扰素马诱导的蛋白质10 (IP-10/CXCL10) 水平的升高显示出与DLBCL风险增加 (IVW方法) 的关联.
DLBCL与巨细胞殖民地刺激因子 (M-CSF),瘤亡因子β (TNF-β) 和与TNF相关的诱导亡的配体 (TRAIL) 的水平增加有相关性.

结论:

这项研究提供了证据,支持在DLBCL发育中特定炎症性细胞因子的因果作用.
MIG/CXCL9和IP-10/CXCL10被确定为DLBCL的潜在上游风险因素.
DLBCL可能导致M-CSF,TNF-β和TRAIL的水平升高,这表明DLBCL预防和治疗的潜在治疗点.

关键词:

DLBCL,扩散大的B细胞淋巴瘤.炎症性细胞因子是炎症性细胞因子.MIG,由干扰素玛诱导的单基因.MR, 门德尔的随机化 TRAIL,与TNF相关的诱导亡的配体.

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