中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (5): 1311-1319.doi: 10.12307/2026.045

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

基因预测731种免疫细胞表型与类风湿性关节炎的关系

刘凤芝1，董玉娜2，田文艺1，王春雷3，梁晓东1，鲍  霖4   

  1. 1山东中医药大学中医学院，山东省济南市   250355；2莱州市人民医院，山东省莱州市   261400；3山东省泰安市王氏正骨医院，山东省泰安市   271000；4中国人民解放军联勤保障部队第九六〇医院，山东省济南市   250031
  • 收稿日期:2024-12-03 接受日期:2025-02-15 出版日期:2026-02-18 发布日期:2025-06-28
  • 通讯作者: Bao Lin, Technologist-in-charge, The 960 Hospital of the Joint Logistics Support Force of the Chinese PLA, Jinan 250031, Shandong Province, China Co-corresponding author: Liang Xiaodong, PhD, Associate professor, Master’s supervisor, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
  • 作者简介:Liu Fengzhi, Master candidate, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China

Gene-predicted associations between 731 immune cell phenotypes and rheumatoid arthritis

Liu Fengzhi1, Dong Yuna2, Tian Wenyi1, Wang Chunlei3, Liang Xiaodong1, Bao Lin4   

  1. 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China; 2Laizhou People’s Hospital, Laizhou 261400, Shandong Province, China; 3Wang Orthopaedic Hospital in Taian, Taian 271000, Shandong Province, China; 4The 960 Hospital of the Joint Logistics Support Force of the Chinese PLA, Jinan 250031, Shandong Province, China
  • Received:2024-12-03 Accepted:2025-02-15 Online:2026-02-18 Published:2025-06-28
  • Contact: 鲍霖，主管技师，中国人民解放军联勤保障部队第九六〇医院，山东省济南市 250031 通讯作者：梁晓东，博士，副教授，硕士生导师，山东中医药大学中医学院，山东省济南市 250355 https://orcid.org/0009-0006-6374-9512 (刘凤芝)
  • About author:刘凤芝，女，山东省菏泽市人，汉族，山东中医药大学在读硕士，主要从事中药学方面的研究。

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摘要：




文题释义：
免疫细胞表型：是指免疫细胞在形态、功能和表面标志等方面的特征。此次研究分析了731种免疫细胞表型，包括绝对细胞计数、表面抗原水平的中位荧光强度、形态学特征和相对细胞计数。这些表型通过全基因组关联研究(GWAS)数据获得，涵盖了B细胞、经典树突状细胞、T细胞、单核细胞、髓系细胞、TBNK细胞(淋巴细胞亚群中的T细胞、B细胞和自然杀伤细胞)和调节性T细胞。
类风湿性关节炎：是一种慢性、进行性自身免疫性疾病，主要影响手足小关节，表现为多关节、对称性、侵袭性关节炎。类风湿性关节炎的特征包括关节外器官受累和血清类风湿因子阳性，可导致关节畸形和功能丧失。类风湿性关节炎的发病机制涉及自身免疫反应、炎症反应、细胞因子的异常产生以及免疫细胞的异常功能。

背景：类风湿性关节炎在世界范围内广泛存在，其高发率和普遍性严重影响了患者的生活质量，以往的研究多集中在少数几种免疫细胞或细胞因子上，而此次研究的全面性为类风湿性关节炎的免疫机制提供了更完整的图景。
目的：采用双向孟德尔随机化方法探讨731种免疫细胞表型与类风湿性关节炎之间的因果关系，并提供一些因果关系的证据。
方法：使用的731种免疫细胞表型来自由美国国立人类基因组研究中心(NHGRI)和欧洲生物信息研究所(EBI)共同开发的GWAScatalog数据库，类风湿性关节炎数据来自由芬兰国家医学基因组中心(FIMM)开发的Finngen数据库。使用逆方差加权法作为主要分析方法，此外，还同时采用了多种分析方法，包括MR-Egger、加权模式、简单模式和加权中位数，以补充最终结果；并对结果进行了敏感性分析(Cochran’s Q检验、MR-Egger回归和MR-presso分析)，以验证数据的稳定性和可行性。
结果与结论：①经过异质性检验分析排除后，逆方差加权法结果表明有10个绝对细胞计数、15个表面抗原水平中位荧光强度、1个形态学特征和9个相对细胞计数与类风湿性关节炎的发生存在因果关系；②根据细胞分类，此次研究发现有7种B细胞、7种经典树突状细胞、6种处于成熟阶段的T细胞、4种单核细胞、3种髓系细胞、3种TBNK(淋巴细胞亚群中的T细胞、B细胞和自然杀伤细胞)和5种调节性T细胞与类风湿性关节炎的发生存在因果关联；③通过全面的双向双样本孟德尔随机化分析，证明了多种免疫表型与类风湿性关节炎之间复杂的因果关系，凸显了免疫系统与类风湿性关节炎之间复杂的相互作用模式，这些成果为国内类风湿性关节炎的早期筛查和诊断提供了新的生物标志物，有助于提高诊断准确性和敏感性。


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 免疫细胞, 免疫细胞表型, 孟德尔随机化, 类风湿性关节炎, 因果关系

Abstract: BACKGROUND: Rheumatoid arthritis is widely prevalent worldwide, with its high incidence and universality that considerably affects patients’ quality of life. Previous studies have focused on a few immune cells or cytokines, whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.
OBJECTIVE: To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method, thereby providing evidence of causality.
METHODS: The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database, jointly developed by the National Human Genome Research Institute (NHGRI) and the European Bioinformatics Institute (EBI). The rheumatoid arthritis data were from the Finngen database, developed by the Finnish Institute for Molecular Medicine (FIMM). The inverse variance weighting method was employed as the primary analytical approach. Additionally, multiple analytical methods, including MR-Egger, weighted mode, simple mode, and weighted median, were concurrently utilized to complement the final results. Sensitivity analyses (Cochran’s Q test, MR-Egger regression, and MR-presso analysis) were also conducted to verify the stability and feasibility of the data.
RESULTS AND CONCLUSION: (1) After excluding results through heterogeneity testing, the inverse variance weighting analysis indicated that 10 absolute cell counts, 15 median fluorescence intensities of surface antigen levels, 1 morphological characteristic, and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis. (2) According to cell classification, this study found that seven types of B cells, seven types of classical dendritic cells, six types of mature T cells, four types of monocytes, three types of myeloid cells, three types of TBNK cells (lymphocyte subset T cells, B cells and natural killer cells), and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis. (3) Through comprehensive bidirectional two-sample MR analysis, we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis, highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis. These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China, and help to improve the diagnostic accuracy and sensitivity.

Key words: immunocyte, immune cell phenotype, Mendelian randomization, rheumatoid arthritis, causal relationship

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