Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Breast Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Immunol. 2024 Sep 27;15:1409545. doi: 10.3389/fimmu.2024.1409545. eCollection 2024.
Previous studies have reported that immunoinflammatory responses have associations with mastitis. Here, we aimed to further figure out whether circulating inflammatory cytokines and immune cells causally impact mastitis liability.
The two-sample Mendelian randomization made use of genetic variances of 91 inflammatory cytokines from a large publicly available genome-wide association study (GWAS) containing 14,824 participants, 731 immunophenotypes data from 3,757 individuals as exposures separately, and mastitis from a GWAS summary (1880 cases and 211699 controls of European ancestry) as outcome. The primary analysis applied the inverse-variance weighted (IVW) method to estimate causal influences, with MR-Egger, weighted median, weighted mode and simple mode as supplementary approaches. Heterogeneity and pleiotropy were evaluated by the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test.
The results indicated that CX3CL1 may be suggestively relevant to the risk of mastitis (odds ratio, OR = 1.434, 95% CI = 1.1421.800, = 0.002). Moreover, three immunophenotypes were identified as having a potential causal link to mastitis ( < 0.05). Significantly, CD28- CD8dim %CD8dim (OR = 1.058, 95% CI = 1.024 ~ 1.093, = 0.0006) and CD45 on CD33br HLA DR+ (OR = 1.097, 95% CI = 1.039 ~ 1.157, = 0.0008) were found to induce mastitis possibly. Conversely, CD39+ secreting Treg AC (OR = 0.929, 95% CI = 0.884 0.978, = 0.005) pertained to protective factors of mastitis. Cochran's Q test and MR-Egger intercept test indicated no significant heterogeneity ( > 0.05) or pleiotropy ( > 0.05), supporting the robustness and reliability of our findings.
Our study adds to current knowledge on the causal roles of inflammatory cytokines and immune cells on mastitis by genetic means, thus guiding future clinical research.
先前的研究表明，免疫炎症反应与乳腺炎有关。在这里，我们旨在进一步研究循环炎症细胞因子和免疫细胞是否会导致乳腺炎易感性。
两样本孟德尔随机化利用来自包含 14824 名参与者的大型公开全基因组关联研究（GWAS）中的 91 种炎症细胞因子的遗传方差，分别将 731 种免疫表型数据（来自 3757 个人）和 GWAS 汇总中的乳腺炎（1880 例病例和 211699 例欧洲血统对照）作为暴露因素进行研究。主要分析采用逆方差加权（IVW）方法来估计因果影响，并用 MR-Egger、加权中位数、加权众数和简单众数作为补充方法。采用 Cochrane Q 检验、MR-Egger 截距检验和 MR-PRESSO 全局检验评估异质性和多效性。
结果表明，CX3CL1 可能与乳腺炎的风险有关（比值比，OR = 1.434，95%CI = 1.1421.800， = 0.002）。此外，还确定了三种免疫表型与乳腺炎有潜在的因果关系（ < 0.05）。重要的是，CD28- CD8dim% CD8dim（OR = 1.058，95%CI = 1.0241.093， = 0.0006）和 CD45 on CD33br HLA DR+（OR = 1.097，95%CI = 1.0391.157， = 0.0008）可能会导致乳腺炎。相反，CD39+分泌 Treg AC（OR = 0.929，95%CI = 0.8840.978， = 0.005）与乳腺炎的保护因素有关。Cochran's Q 检验和 MR-Egger 截距检验表明没有显著的异质性（ > 0.05）或多效性（ > 0.05），支持我们研究结果的稳健性和可靠性。
本研究通过遗传手段增加了炎症细胞因子和免疫细胞对乳腺炎的因果作用的现有知识，从而为未来的临床研究提供了指导。
