Wang Wencai, Ma Luyao, Liu Menghao, Zhao Yongqiang, Ye Wei, Li Xianfeng
The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China.
BMC Neurol. 2025 Mar 8;25(1):98. doi: 10.1186/s12883-025-04098-4.
Previous studies have suggested a possible link between normal pressure hydrocephalus (NPH) and immune factors, but the causal relationship between NPH and Baff-R expression on immune cells remains enigmatic. This study used a Mendelian randomization (MR) method to elucidate this association.
The study used data from the Finngen genome-wide association study (GWAS) and included a large European cohort of 767 patients with NPH and 375,610 controls. Baff-R genetic results in 3,757 individuals of European ancestry had 22 Baff-R-related traits. Different MR techniques were used, and efficacy was assessed using heterogeneity and sensitivity analyses.
Among the 22 traits, 8 Baff-R-related traits were causally related to NPH. The genetic prediction indicates that Baff-R, particularly in the area of BAFF - R on unswitched memory B cell, BAFF - R on IgD + CD38 - B cell, BAFF - R on CD24 + CD27 + B cell, BAFF - R on IgD - CD38 - B cell, BAFF - R on IgD + CD38dim B cell, BAFF - R on IgD + CD24 + B cell, BAFF - R on IgD + CD38 - naive B cell, BAFF - R on memory B cell may decrease risks on the development of NPH. These findings may help us to understand the immune mechanisms associated with NPH and help to develop future biomarkers related to the disease.
以往研究提示正常压力脑积水（NPH）与免疫因子之间可能存在联系，但NPH与免疫细胞上Baff-R表达之间的因果关系仍不明确。本研究采用孟德尔随机化（MR）方法来阐明这种关联。
本研究使用了芬兰基因组全基因组关联研究（GWAS）的数据，纳入了一个大型欧洲队列，其中包括767例NPH患者和375,610名对照。3757名欧洲血统个体的Baff-R基因结果有22个与Baff-R相关的性状。使用了不同的MR技术，并通过异质性和敏感性分析评估效能。
在这22个性状中，8个与Baff-R相关的性状与NPH存在因果关系。遗传预测表明，Baff-R，特别是未转换记忆B细胞上的BAFF-R、IgD+CD38-B细胞上的BAFF-R、CD24+CD27+B细胞上的BAFF-R、IgD-CD38-B细胞上的BAFF-R、IgD+CD38dim B细胞上的BAFF-R、IgD+CD24+B细胞上的BAFF-R、IgD+CD38-幼稚B细胞上的BAFF-R、记忆B细胞上的BAFF-R可能会降低NPH发生的风险。这些发现可能有助于我们理解与NPH相关的免疫机制，并有助于开发与该疾病相关的未来生物标志物。
