Zheng Kaiyuan, Wang Siyu, Zeng Lianlin, Li Yangan, Hu Kehui
Department of Rehabilitation Medicine, Intensive Care Unit, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P.R.China.
Department of Rehabilitation Medicine, Suining Central Hospital, Suining, Sichuan, P.R.China.
Medicine (Baltimore). 2024 Dec 13;103(50):e40894. doi: 10.1097/MD.0000000000040894.
The influence of circulating white blood cells and inflammatory factors on pruritus is gradually recognized by the public, but the specific causal relationship is still unknown. In this study, we included inflammatory cytokine profiles from 8293 healthy subjects, genetic data on blood cells from various ethnic and ancestry backgrounds, including 746,667 individuals, and 1370 patients of European descent with pruritus for a bidirectional 2-sample Mendelian randomization (MR) analysis. We employed several robust statistical methods, including the inverse variance weighted, weighted median, and the MR-Egger method. We further refined our analysis through a meticulous sensitivity assessment using the leave-one-out strategy, evaluated the heterogeneity of our findings using Cochran's Q test, and addressed potential pleiotropic effects through the MR-Egger intercept test. Ultimately, a reverse MR analysis was conducted to assess the potential for reverse causation. Genetic prediction data indicate a positive correlation between eosinophil cell count and the risk of developing pruritus (odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.09-1.55, P = .003). Furthermore, elevated levels of stromal-cell-derived factor 1 alpha (OR = 1.80, 95% CI: 1.15-2.77, P = .009), monokine induced by gamma interferon (OR = 1.23, 95% CI: 1.04-1.46, P = .015), and cutaneous T-cell-attracting chemokine (OR = 1.24, 95% CI: 1.01-1.53, P = .043) are all associated with an increased risk of pruritus occurrence, respectively. No evidence of horizontal pleiotropy or heterogeneity was observed among the genetic variants (P > .05), and the leave-one-out analysis confirmed the stability and robustness of this association. The reverse MR analysis demonstrated the absence of reverse causality. Our research delineates the causal links between eosinophil cell count, stromal-cell-derived factor 1 alpha, monokine induced by gamma interferon, cutaneous T-cell-attracting chemokine levels, and pruritus susceptibility. These insights may present promising avenues for enhancing the management and therapeutic strategies for patients suffering from pruritus.
循环白细胞和炎症因子对瘙痒的影响逐渐为公众所认识，但其具体因果关系仍不清楚。在本研究中，我们纳入了8293名健康受试者的炎症细胞因子谱、来自不同种族和血统背景的746,667人的血细胞基因数据，以及1370名欧洲血统的瘙痒患者，进行双向双样本孟德尔随机化（MR）分析。我们采用了几种稳健的统计方法，包括逆方差加权法、加权中位数法和MR-Egger法。我们通过使用留一法策略进行细致的敏感性评估进一步完善了分析，使用 Cochr an's Q检验评估研究结果的异质性，并通过MR-Egger截距检验解决潜在的多效性效应。最终，进行了反向MR分析以评估反向因果关系的可能性。基因预测数据表明嗜酸性粒细胞计数与发生瘙痒的风险呈正相关（优势比[OR]=1.31，95%置信区间[CI]=1.09-1.55，P=0.003）。此外，基质细胞衍生因子1α水平升高（OR=1.80，95%CI：1.15-2.77，P=0.009）、γ干扰素诱导的单核因子（OR=1.23，95%CI：1.04-1.46，P=0.015）和皮肤T细胞吸引趋化因子（OR=1.24，95%CI：1.01-1.53，P=0.043）均分别与瘙痒发生风险增加相关。在基因变异中未观察到水平多效性或异质性的证据（P>0.05），留一法分析证实了这种关联的稳定性和稳健性。反向MR分析表明不存在反向因果关系。我们的研究描绘了嗜酸性粒细胞计数、基质细胞衍生因子1α、γ干扰素诱导的单核因子、皮肤T细胞吸引趋化因子水平与瘙痒易感性之间的因果联系。这些见解可能为改善瘙痒患者的管理和治疗策略提供有前景的途径。
