Nian Sunqi, Wang Kui, Wang Jiawei, Wang Suijian, Li Chengjin, Li Na, Chen Jiayu
The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
The First Clinical College of Shandong University, Jinan, Shandong, China.
Ann Vasc Surg. 2025 May;114:126-132. doi: 10.1016/j.avsg.2025.01.030. Epub 2025 Jan 28.
Varicose veins (VVs) are a common chronic venous disorder with a complex pathophysiology involving immune dysregulation, inflammation, and genetic predisposition. This study aims to identify immune-related causal factors in the pathogenesis of VVs using Mendelian randomization (MR).
A 2-sample MR analysis was conducted to assess the causal relationships between immune cell phenotypes and VVs. Genetic variants were used as instrumental variables, and data were derived from the Finland and genome-wide association study catalog. Inverse variance weighting (IVW) was used as the primary method, supported by sensitivity analyses such as MR-Egger, weighted median, and weighted mode.
A total of 79 immunophenotypes were identified as significantly associated with VVs, including 19 related to B-cells, 6 to conventional dendritic cells, 6 to T-cell maturation stages, 6 to monocytes, 12 to myeloid cells, 11 to T cells, B cells, and natural killer cells, and 17 to regulatory T-cells (Tregs). Of these, 8 immunophenotypes remained significant after multiple testing correction (false discovery rate <0.05). Specifically, high expression of cluster of differentiation 86 (CD86) on myeloid dendritic cells, CD33 expression on myeloid cells (e.g., basophils and human leukocyte antigen DR + subsets), increased side scatter area (SSC-A) on lymphocytes, and associations with CD39+ Tregs showed significant correlations with VVs.
This study highlights the involvement of immune cells in the pathogenesis of VVs. High expression of CD86 on myeloid DCs and SSC-A on lymphocytes may serve as potential markers for predicting VVs risk, while the protective role of CD39+ Tregs suggests a new direction for immune modulation therapy. Further research is needed to validate these findings across diverse populations and explore their clinical applications.
静脉曲张（VVs）是一种常见的慢性静脉疾病，其病理生理过程复杂，涉及免疫失调、炎症和遗传易感性。本研究旨在利用孟德尔随机化（MR）确定静脉曲张发病机制中与免疫相关的因果因素。
进行两样本MR分析，以评估免疫细胞表型与静脉曲张之间的因果关系。将基因变异用作工具变量，数据来源于芬兰和全基因组关联研究目录。采用逆方差加权（IVW）作为主要方法，并通过MR-Egger、加权中位数和加权模式等敏感性分析加以支持。
共确定79种免疫表型与静脉曲张显著相关，其中19种与B细胞相关，6种与传统树突状细胞相关，6种与T细胞成熟阶段相关，6种与单核细胞相关，12种与髓细胞相关，11种与T细胞、B细胞和自然杀伤细胞相关，17种与调节性T细胞（Tregs）相关。其中，经过多重检验校正后，8种免疫表型仍具有显著性（错误发现率<0.05）。具体而言，髓样树突状细胞上分化簇86（CD86）的高表达、髓细胞（如嗜碱性粒细胞和人类白细胞抗原DR +亚群）上CD33的表达、淋巴细胞上侧向散射面积（SSC-A）增加以及与CD39 + Tregs的关联与静脉曲张显示出显著相关性。
本研究强调了免疫细胞在静脉曲张发病机制中的作用。髓样树突状细胞上CD86的高表达和淋巴细胞上SSC-A可能作为预测静脉曲张风险的潜在标志物，而CD39 + Tregs的保护作用为免疫调节治疗指明了新方向。需要进一步研究以在不同人群中验证这些发现并探索其临床应用。
