Abstract
INTRODUCTION: Immune cells are involved in the onset and progression of Sjögren's syndrome (SS). This study explored the causal relationship between immune signature cells and SS, which has not been fully elucidated. METHODS: We conducted univariate, multivariate, and bidirectional Mendelian randomization to investigate the causal relationship between 731 immunological feature characteristic cells and SS pairs and explore the interaction of immune cells in SS. RESULTS: After false discovery rate correction, six immune cells were significantly associated with SS risk. Among them, four contributed to SS (CD24 on memory B cell, CD27 on IgD + CD24 + B cell, CD28 on CD39+ secreting CD4 Treg cell, and CD80 on CD62L + mDC); two appeared to reduce SS risk (CD3 on CD39 + CD8 + T cell and CD38 on IgD + CD38 + B cell). Pleiotropy and heterogeneity were not observed. Three immune cells exerted independent effects for SS (CD27 on IgD + CD24 + B cell, CD80 on CD62L + mDC, and CD38 on IgD + CD38 + B cell); two were risk factors (CD27 on IgD + CD24 + B cell and CD80 on CD62L + mDC); and one was a protective factor (CD38 on IgD + CD38 + B cell). Twenty-three immune cells showed a reverse causal relationship with SS. CONCLUSION: These findings demonstrate the influence of immune cells on SS risk and the effects of SS on immune cells, providing new clues for further research on the mechanisms underlying SS.