Yu Yunfeng, Yang Xinyu, Hu Gang, Yin Yuman, Yu Rong
School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.
Department of Endocrinology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
Front Psychiatry. 2024 May 16;15:1397006. doi: 10.3389/fpsyt.2024.1397006. eCollection 2024.
The role of different immune cells in autism spectrum disorders (ASD) is still controversial. The purpose of this study was to evaluate the causal effects of different immune cell phenotypes on ASD via Mendelian randomization (MR).
Datasets of immune cell phenotypes were obtained from the European Bioinformatics Institute, and datasets of ASD were obtained from the IEU Open GWAS project. Single nucleotide polymorphisms were selected based on the assumptions of association, independence, and exclusivity. Inverse variance weighted was utilized as the main method for MR analysis. MR-Egger was employed to assess the horizontal pleiotropy of the results. Cochran's Q and leave-one-out method were used for heterogeneity analysis and sensitivity analysis of the results, respectively.
MR analysis showed that TD CD8br AC [odds ratio (OR), 1.137; 95% confidence interval (CI), 1.031-1.254; = 0.010], CD8br %leukocyte (OR, 1.142; 95% CI, 1.067-1.223; < 0.001), CD8br and CD8dim %leukocyte (OR, 1.117; 95% CI, 1.032-1.210; = 0.006), naive CD8br %T cell (OR, 1.052; 95% CI, 1.004-1.104; = 0.035), CD28- CD8dim %T cell (OR, 1.097; 95% CI, 1.038-1.158; < 0.001), CD127- CD8br AC (OR, 1.086; 95% CI, 1.006-1.171; = 0.034), CD45 on CD8br (OR, 1.059; 95% CI, 1.021-1.099; = 0.002), CD3 on HLA DR+ CD8br (OR, 1.098; 95% CI, 1.041-1.158; < 0.001), CD4 on activated Treg (OR, 1.048; 95% CI, 1.001-1.096; = 0.046), CD3 on CD39+ resting Treg (OR, 1.070; 95% CI, 1.012-1.131; = 0.018), IgD+ CD38- %lymphocyte (OR, 1.103; 95% CI, 1.023-1.190; = 0.011), CD62L- plasmacytoid DC %DC (OR, 1.046; 95% CI, 1.001-1.093; = 0.046), and FSC-A on plasmacytoid DC (OR, 1.075; 95% CI, 1.003-1.153; = 0.042) were associated with increased genetic susceptibility to ASD. MR-Egger displayed no horizontal pleiotropy ( ≥ 0.05). Cochran's Q revealed no heterogeneity of results ( ≥ 0.05). Sensitivity analysis indicated that the results were robust.
This MR analysis revealed 13 immune cell phenotypes associated with increased genetic susceptibility to ASD and emphasized the importance of CD8 T cells and Tregs, which provides new directions for the pathogenesis and drug research of ASD.
不同免疫细胞在自闭症谱系障碍（ASD）中的作用仍存在争议。本研究的目的是通过孟德尔随机化（MR）评估不同免疫细胞表型对ASD的因果效应。
免疫细胞表型数据集来自欧洲生物信息学研究所，ASD数据集来自IEU开放GWAS项目。基于关联性、独立性和排他性的假设选择单核苷酸多态性。采用逆方差加权作为MR分析的主要方法。采用MR-Egger评估结果的水平多效性。分别使用Cochran's Q和留一法进行结果的异质性分析和敏感性分析。
MR分析显示，TD CD8br AC[比值比（OR），1.137；95%置信区间（CI），1.031-1.254；P = 0.010]、CD8br%白细胞（OR，1.142；95%CI，1.067-1.223；P < 0.001）、CD8br和CD8dim%白细胞（OR，1.117；95%CI，1.032-1.210；P = 0.006）、幼稚CD8br%T细胞（OR，1.052；95%CI，1.004-1.104；P = 0.035）、CD28-CD8dim%T细胞（OR，1.097；95%CI，1.038-1.158；P < 0.001）、CD127-CD8br AC（OR，1.086；95%CI，1.006-1.171；P = 0.034）、CD8br上的CD45（OR，1.059；95%CI，1.021-1.099；P = 0.002）、HLA DR+CD8br上的CD3（OR，1.098；95%CI，1.041-1.158；P < 0.001）、活化Treg上的CD4（OR，1.048；95%CI，1.001-1.096；P = 0.046）、CD39+静息Treg上的CD3（OR，1.070；95%CI，1.012-1.131；P = 0.018）、IgD+CD38-%淋巴细胞（OR，1.103；95%CI，1.023-1.190；P = 0.011）、CD62L-浆细胞样DC%DC（OR，1.046；95%CI，1.001-1.093；P = 0.046）以及浆细胞样DC上的FSC-A（OR，1.075；95%CI，1.003-1.153；P = 0.042）与ASD遗传易感性增加相关。MR-Egger显示无水平多效性（P≥0.05）。Cochran's Q显示结果无异质性（P≥0.05）。敏感性分析表明结果具有稳健性。
本MR分析揭示了13种与ASD遗传易感性增加相关的免疫细胞表型，并强调了CD8 T细胞和调节性T细胞的重要性，为ASD的发病机制和药物研究提供了新方向。
