Mendelian Randomization Study on Causal Associations Between Immunophenotypes and Acute Pancreatitis

LU Ting; GAN Hongjun; LIU Tao

doi:10.13919/j.issn.2095-6274.ZHJY202504050

Abstract：Objective To investigate the causal relationship between immunophenotypes and the risk of disease onset,specifically acute pancreatitis,using a two-sample Mendelian randomization approach.Methods Data on 731 immune cell phenotypes and acute pancreatitis were obtained from the FinnGen database and GWAS catalog.The in-verse-variance weighted method,weighted median method,and MR-Egger regression were employed to examine the causal links.The robustness and reliability of the findings were assessed via Cochran's Q test,MR-Egger regression,MR-PRESSO,leave-one-out analysis,and meta-analysis.Results Thirty-four immunophenotypes showed potential causal associations(P<0.05).After Bonferroni correction,ten phenotypes demonstrated significant associations.Among these,seven effector phenotypes(CD19 on CD20-,FSC-A on NKT,CD4 on CD39+CD4+,CD19 on IgD+CD24+,CD25hi CD45RA-CD4 not Treg%CD4+,HLA DR on B cell,CD39 on CD39+CD4+)(OR:1.18～1.41)were significantly asso-ciated with increased risk,while three protective phenotypes(CD28+CD45RA+CD8br%CD8br,CD62L-plasmacytoid DC AC,CD127-CD8br%CD8br)(OR:0.68～0.82)showed a negative association trend(P<6.8×10⁻⁵).Key risk markers included CD19+/CD20-B cells(β=0.26,PIVW=3.8×10⁻⁴)and HLA-DR+B cells(β=0.18,PIVW=6.2×10⁻⁶).Conclusion This two-sample Mendelian randomization study identified ten immunophe-notypes significantly associated with acute pancreatitis(CD19 on CD20-,FSC-A on NKT,CD4 on CD39+CD4+,CD19 on IgD+CD24+,CD25hi CD45RA-CD4 not Treg%CD4+,HLA DR on B cell,CD39 on CD39+CD4+,CD28+CD45RA+CD-8br%CD8br,CD62L-plasmacytoid DC AC,CD127-CD8br%CD8br),providing genetic evidence for understanding its immunoregulatory mechanisms and potential therapeutic targets.