Yang Liu, Jie Kang, Yazhen Su, Xiuying Fan, Dan Ma, Zewen Wu, Xueyan Gong, Junkang Zhao, Liyun Zhang
{"title":"免疫细胞在原发性斯约格伦综合征中的因果作用：双样本孟德尔随机试验","authors":"Yang Liu, Jie Kang, Yazhen Su, Xiuying Fan, Dan Ma, Zewen Wu, Xueyan Gong, Junkang Zhao, Liyun Zhang","doi":"10.1111/1756-185X.15350","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by the destruction of exocrine glands primarily via T-cell-mediated B-cell over-activation and cytokine production. This leads to pronounced dryness of the mouth and eyes and can result in multi-systemic involvement affecting the kidneys, lungs, and blood. In recent years, there has been increasing attention on the role of immune cells in pSS. However, studies investigating the causal role of immune cells in pSS have been relatively limited.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>In this study, we employed a two-way two-sample Mendelian randomization approach to assess the causal relationship between immune cells and pSS. Utilizing publicly available genome-wide association study (GWAS) data, we explored the causal links between 731 immunophenotypically labeled immune cells and the risk of pSS.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Through the use of instrumental variables derived from GWAS data and corrected for false discovery rate (FDR), we identified three immune cells with increased levels that were causally associated with pSS risk (FDR < 0.05). These included IgD+ CD38br AC B cells, CD27 on IgD+ CD38− unswitched memory B cells, and Granulocyte % leukocyte. Additionally, three immune cells with reduced levels were found to be causally associated with pSS risk, namely CD4+ CD8dim %lymphocyte, CD4+ CD8dim %leukocyte, and CD28 on activated and secreting regulatory T cells (Tregs). Furthermore, the development of pSS was associated with elevated levels of CD33br HLA DR+ CD14− % CD33br HLA DR+ in myeloid cells.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This study demonstrates that immune responses influence the progression of pSS in a complex pattern. Our findings may provide new insights into the immunology of pSS pathogenesis and more experimental studies should be conducted to further explore the potential mechanisms between identified immune features and pSS risk, which may provide a basis for exploring early intervention methods for pSS and developing targeted therapeutic strategies or even reshaping immune homeostasis.</p>\n </section>\n </div>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"27 11","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The causal role of immune cells in primary Sjögren's syndrome: A two-sample Mendelian randomization\",\"authors\":\"Yang Liu, Jie Kang, Yazhen Su, Xiuying Fan, Dan Ma, Zewen Wu, Xueyan Gong, Junkang Zhao, Liyun Zhang\",\"doi\":\"10.1111/1756-185X.15350\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by the destruction of exocrine glands primarily via T-cell-mediated B-cell over-activation and cytokine production. This leads to pronounced dryness of the mouth and eyes and can result in multi-systemic involvement affecting the kidneys, lungs, and blood. In recent years, there has been increasing attention on the role of immune cells in pSS. However, studies investigating the causal role of immune cells in pSS have been relatively limited.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>In this study, we employed a two-way two-sample Mendelian randomization approach to assess the causal relationship between immune cells and pSS. Utilizing publicly available genome-wide association study (GWAS) data, we explored the causal links between 731 immunophenotypically labeled immune cells and the risk of pSS.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Through the use of instrumental variables derived from GWAS data and corrected for false discovery rate (FDR), we identified three immune cells with increased levels that were causally associated with pSS risk (FDR < 0.05). These included IgD+ CD38br AC B cells, CD27 on IgD+ CD38− unswitched memory B cells, and Granulocyte % leukocyte. Additionally, three immune cells with reduced levels were found to be causally associated with pSS risk, namely CD4+ CD8dim %lymphocyte, CD4+ CD8dim %leukocyte, and CD28 on activated and secreting regulatory T cells (Tregs). Furthermore, the development of pSS was associated with elevated levels of CD33br HLA DR+ CD14− % CD33br HLA DR+ in myeloid cells.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>This study demonstrates that immune responses influence the progression of pSS in a complex pattern. 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The causal role of immune cells in primary Sjögren's syndrome: A two-sample Mendelian randomization
Background
Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by the destruction of exocrine glands primarily via T-cell-mediated B-cell over-activation and cytokine production. This leads to pronounced dryness of the mouth and eyes and can result in multi-systemic involvement affecting the kidneys, lungs, and blood. In recent years, there has been increasing attention on the role of immune cells in pSS. However, studies investigating the causal role of immune cells in pSS have been relatively limited.
Methods
In this study, we employed a two-way two-sample Mendelian randomization approach to assess the causal relationship between immune cells and pSS. Utilizing publicly available genome-wide association study (GWAS) data, we explored the causal links between 731 immunophenotypically labeled immune cells and the risk of pSS.
Results
Through the use of instrumental variables derived from GWAS data and corrected for false discovery rate (FDR), we identified three immune cells with increased levels that were causally associated with pSS risk (FDR < 0.05). These included IgD+ CD38br AC B cells, CD27 on IgD+ CD38− unswitched memory B cells, and Granulocyte % leukocyte. Additionally, three immune cells with reduced levels were found to be causally associated with pSS risk, namely CD4+ CD8dim %lymphocyte, CD4+ CD8dim %leukocyte, and CD28 on activated and secreting regulatory T cells (Tregs). Furthermore, the development of pSS was associated with elevated levels of CD33br HLA DR+ CD14− % CD33br HLA DR+ in myeloid cells.
Conclusion
This study demonstrates that immune responses influence the progression of pSS in a complex pattern. Our findings may provide new insights into the immunology of pSS pathogenesis and more experimental studies should be conducted to further explore the potential mechanisms between identified immune features and pSS risk, which may provide a basis for exploring early intervention methods for pSS and developing targeted therapeutic strategies or even reshaping immune homeostasis.
期刊介绍：
The International Journal of Rheumatic Diseases (formerly APLAR Journal of Rheumatology) is the official journal of the Asia Pacific League of Associations for Rheumatology. The Journal accepts original articles on clinical or experimental research pertinent to the rheumatic diseases, work on connective tissue diseases and other immune and allergic disorders. The acceptance criteria for all papers are the quality and originality of the research and its significance to our readership. Except where otherwise stated, manuscripts are peer reviewed by two anonymous reviewers and the Editor.
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