<b>A Mendelian randomization study on the causal role of immune cells in chronic pancreatitis</b>

<p dir="ltr"><i>Background:</i>Chronic pancreatitis (CP) is recognized as a risk factor for pancreatic tumors. The diagnostic difficulty of this disease is due to unclear pathological features and a lack of clinically recognized disease staging.The immune system, playing a crucial role in the pathogenesis of chronic pancreatitis, may exert its influence from the early to late stages of the condition.</p><p dir="ltr"><b><i>Method:</i></b><b> </b>This study delves into the causal relationship between immune cell characteristics (such as median fluorescence intensity (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) and chronic pancreatitis using a two-sample Mendelian randomization (MR) analysis. A comprehensive sensitivity analysis has been applied to ensure the robustness, heterogeneity, and absence of horizontal pleiotropy in the results.</p><p dir="ltr"><b><i>Result:</i></b><b> </b>A total of 30 suggestive immune phenotypes were identified in the MR analysis of two samples. We found that the onset of CP can increase the level of IgD+AC on B cells, CD25hi CD45RA CD4 not Treg AC on Treg cells, CD14+CD16+monocyte AC on monocyte, CD4+% T cells increase in TBNK, DP (CD4+CD8+)% Leukocyte in TBNK, IgD+CD24+levels on B cells, CD20 on IgD+CD38dim levels in B cells, CD24 on transient levels in B cells, CD25 on IgD+CD38 naive in B cells, CD25 on IgD CD38- on B cells, IgD on transient levels, CD28 on CD28+DN (CD4-CD8-) in Treg. IgD CD38dim% B cellreduction, CM DN (CD4-CD8-)% DN levels on Matura stages of T cells, CD8br AC in TBNK, CD4+CD8 dim% lymphocyte ratio in TBNK, Granuloceyte% leukoceyte in TBNK, CD39+CD8br% T cell in Treg, CD38 on IgD CD38br levels on B cells, CD62L on CD62L+myoid DC in cDC cells, HVEM on EM CD4+in Matura stages of T cells and CD28 on CD28+and CD4+in Treg were significantly reduced in CP patients.</p><p dir="ltr"><b><i>Conclusion:</i></b><i> </i>Through a bidirectional Mendelian randomization (MR) analysis, we have substantiated the causal relationship between various immune phenotypes and chronic pancreatitis (CP).</p>