Hua Danyun, Wang Lu, Li Na, Xu Xiang, Yin Xiaohu
Fenghua Hospital of Traditional Chinese Medicine, Ningbo, Zhejiang Province, China.
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
Medicine (Baltimore). 2024 Dec 13;103(50):e40892. doi: 10.1097/MD.0000000000040892.
This study explores the hidden connection between HLA DR on CD14- CD16+ monocytes and ankylosing spondylitis (AS), with a particular emphasis on investigating and measuring the impact of 1091 blood metabolites as potential mediators. We harnessed the power of summary-level data extracted from a comprehensive genome-wide association study to delve into the intricate relationship between genetically predicted HLA DR on CD14- CD16+ monocytes (3621 cases) and AS (1193 cases and 374,621 controls). Furthermore, we employed a two-step Mendelian randomization (MR) methodology to elucidate the extent to which blood metabolites contribute to the effects observed in CD14- CD16+ monocytes, ultimately influencing the development of AS. This methodological approach provides a comprehensive and rigorous exploration of the interplay between blood metabolites and AS, shedding light on the underlying mechanisms governing this intricate association. Through MR analysis, our investigation revealed an increase in HLA DR on CD14- CD16+ monocytes within plasma, which correspondingly led to a reduction in the incidence of AS. The primary MR analysis yielded an odds ratio of 0.64 with a 95% confidence interval spanning from 0.53 to 0.78, underscoring the protective effect of elevated HLA DR on CD14- CD16+ monocytes against the development of AS. Furthermore, our study found no compelling evidence to suggest that AS exerts any discernible influence on HLA DR on CD14- CD16+ monocytes. Instead, our investigation identified N6, N6, N6-trimethyllysine levels (TML), a blood metabolite, as the sole mediator in the relationship between HLA DR on CD14- CD16+ monocytes and AS. Notably, the genetic prediction of AS mediated by TML accounted for a substantial -2.98% proportion of the observed variance. Our investigation has delineated a causal association between HLA DR on CD14- CD16+ monocytes and AS. Specifically, HLA DR on CD14- CD16+ monocytes exhibited a protective effect against the development of AS. Conversely, AS mediated by TML emerged as a risk factor, though the precise impact of HLA DR on CD14- CD16+ monocytes on AS pathogenesis remains enigmatic. It is imperative to embark on further investigations into potential mediators. In a clinical setting, it is imperative to carefully monitor the patient's HLA DR on CD14- CD16+ monocytes levels.
本研究探讨了CD14-CD16+单核细胞上的人类白细胞抗原DR（HLA DR）与强直性脊柱炎（AS）之间的潜在联系，特别着重于研究和测量1091种血液代谢物作为潜在介导因子的影响。我们利用从一项全面的全基因组关联研究中提取的汇总水平数据，深入探究基因预测的CD14-CD16+单核细胞上的HLA DR（3621例）与AS（1193例和374,621例对照）之间的复杂关系。此外，我们采用了两步孟德尔随机化（MR）方法，以阐明血液代谢物在CD14-CD16+单核细胞中所观察到的效应中所起作用的程度，最终影响AS的发展。这种方法全面而严谨地探索了血液代谢物与AS之间的相互作用，揭示了控制这种复杂关联的潜在机制。通过MR分析，我们的研究发现血浆中CD14-CD16+单核细胞上的HLA DR增加，这相应地导致AS发病率降低。初步MR分析得出的比值比为0.64，95%置信区间为0.53至0.78，强调了CD14-CD16+单核细胞上HLA DR升高对AS发展的保护作用。此外，我们的研究没有发现有力证据表明AS对CD14-CD16+单核细胞上的HLA DR有任何明显影响。相反，我们的研究确定血液代谢物N6,N6,N6-三甲基赖氨酸水平（TML）是CD14-CD16+单核细胞上的HLA DR与AS之间关系的唯一介导因子。值得注意 的是，由TML介导的AS的基因预测占观察到的变异的相当大比例，为-2.98%。我们的研究描绘了CD14-CD16+单核细胞上的HLA DR与AS之间的因果关联。具体而言，CD14-CD16+单核细胞上的HLA DR对AS的发展具有保护作用。相反，由TML介导的AS则是一个危险因素，尽管CD14-CD16+单核细胞上的HLA DR对AS发病机制的确切影响仍然不明。必须对潜在的介导因子展开进一步研究。在临床环境中，必须仔细监测患者CD14-CD16+单核细胞上的HLA DR水平。
