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Exploring the immunological landscape of osteomyelitis through mendelian randomization analysis
Frontiers in Genetics ( IF 3.7 ) Pub Date : 2024-04-08 , DOI: 10.3389/fgene.2024.1362432
Kehan Long , Ao Gong , Dou Yu , Sumiao Dong , Zhendong Ying , Lei Zhang

Background:Osteomyelitis is a severe bone marrow infection, whose pathogenesis is not yet fully understood. This study aims to explore the causal relationship between immune cell characteristics and osteomyelitis, hoping to provide new insights for the prevention and treatment of osteomyelitis.Methods:Based on two independent samples, this study employed a two-sample Mendelian randomization (MR) analysis to assess the causal relationship between 731 immune cell characteristics (divided into seven groups) and osteomyelitis. Genetic variants were used as proxies for risk factors to ensure that the selected instrumental variables meet the three key assumptions of MR analysis. Genome-Wide Association Studies (GWAS) data for immune characteristics were obtained from the public GWAS catalog, while data for osteomyelitis was sourced from the FinnGen.Results:At a significance level of 0.05, 21 immune phenotypes were identified as having a causal relationship with osteomyelitis development. In the B cell group, phenotypes such as Memory B cell % B cell (percentage of memory B cells within the total B cell population, % finger cell ratio), CD20 %B cell (percentage of B cells that do not express the CD20 marker on their surface), and Memory B cell % lymphocyte showed a positive causal relationship with osteomyelitis, while Naive-mature B cell %B cell and IgD-CD38-absolute cell counts (AC) phenotypes showed a negative causal relationship. In addition, specific immune phenotypes in the conventional dendritic cells (cDCs) group, Myeloid cell group, TBNK (T cells, B cells, natural killer cells) cell group, T cell maturation stage, and Treg cell group also showed significant associations with osteomyelitis. Through reverse MR analysis, it was found that osteomyelitis had no significant causal impact on these immune phenotypes, suggesting that the occurrence of osteomyelitis may not affect these immune cell phenotypes.Conclusion:To our knowledge, this is the first study to shed light on the causal relationship between specific immune cell characteristics and the development of osteomyelitis, thereby providing a new perspective to understand the immune mechanism of osteomyelitis. These findings are significant for formulating targeted prevention and treatment strategies, and hold promise to improve the treatment outcomes for patients with osteomyelitis.

中文翻译:

通过孟德尔随机分析探索骨髓炎的免疫学景观

背景:骨髓炎是一种严重的骨髓感染,其发病机制尚不完全清楚。本研究旨在探讨免疫细胞特征与骨髓炎之间的因果关系,希望为骨髓炎的防治提供新的见解。方法:本研究基于两个独立样本,采用两样本孟德尔随机化(MR)分析,评估 731 个免疫细胞特征(分为七组)与骨髓炎之间的因果关系。遗传变异被用作风险因素的代理,以确保所选的工具变量满足 MR 分析的三个关键假设。免疫特征的全基因组关联研究 (GWAS) 数据来自公共 GWAS 目录,而骨髓炎的数据来自 FinnGen。 结果:在显着性水平为 0.05 时,21 种免疫表型被确定为与骨髓炎的发展。在 B 细胞组中,表型如记忆 B 细胞 % B 细胞(记忆 B 细胞占总 B 细胞群的百分比,% 手指细胞比例)、CD20-B 细胞百分比(表面不表达 CD20 标记物的 B 细胞百分比)和记忆 B 细胞百分比淋巴细胞与骨髓炎呈正因果关系,而幼稚成熟 B 细胞百分比和 IgD-CD38 绝对细胞百分比计数(AC)表型显示负因果关系。此外,常规树突状细胞(cDC)组、髓样细胞组、TBNK(T细胞、B细胞、自然杀伤细胞)细胞组、T细胞成熟阶段、Treg细胞组的特异性免疫表型也与骨髓炎存在显着相关性。 。通过反向MR分析,发现骨髓炎对这些免疫表型没有显着的因果影响,提示骨髓炎的发生可能不会影响这些免疫细胞表型。结论:据我们所知,这是第一个阐明骨髓炎的研究特异性免疫细胞特征与骨髓炎发生之间的因果关系,从而为理解骨髓炎的免疫机制提供了新的视角。这些发现对于制定有针对性的预防和治疗策略具有重要意义,有望改善骨髓炎患者的治疗结果。
更新日期:2024-04-08
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