A causal relationship between distinct immune features and acute or chronic pancreatitis: results from a mendelian randomization analysis

Rujuan Liu; Kui Wang; Xiaoyu Guo; Qiqi Wang; Xiuli Zhang; Kaixin Peng; Wanyi Lu; Zhigao Chen; Feng Cao; Zheng Wang; Li Wen

doi:10.1016/j.pan.2024.10.006

A causal relationship between distinct immune features and acute or chronic pancreatitis: results from a mendelian randomization analysis

Pancreatology. 2024 Oct 11:S1424-3903(24)00756-7. doi: 10.1016/j.pan.2024.10.006. Online ahead of print.

Authors

Rujuan Liu¹, Kui Wang², Xiaoyu Guo³, Qiqi Wang⁴, Xiuli Zhang³, Kaixin Peng³, Wanyi Lu³, Zhigao Chen³, Feng Cao⁵, Zheng Wang⁶, Li Wen⁷

Affiliations

¹ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shanxi Province, China; Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH) & State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
² Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH) & State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
⁴ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shanxi Province, China.
⁵ Department of General Surgery, Xuanwu Hospital Capital Medical University, Beijing, China.
⁶ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shanxi Province, China. Electronic address: zheng.wang11@xjtu.edu.cn.
⁷ Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH) & State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. Electronic address: wenli7007@gmail.com.

PMID: 39419750
DOI: 10.1016/j.pan.2024.10.006

Abstract

Objectives: This study aimed to thoroughly examining the causal link between immune traits and four types of pancreatitis, using mendelian randomization.

Methods: Data on 731 immune traits were collected from the genome-wide association study (GWAS) database as exposure. Information regarding acute pancreatitis (AP), alcohol-induced acute pancreatitis (AAP), chronic pancreatitis (CP), and alcohol-induced chronic pancreatitis (ACP) were acquired from the FinnGen Consortium as outcomes. Mendelian randomization (MR) using inverse variance weighting (IVW) evaluated the links between immune traits and pancreatitis. We evaluated the robustness of the IVW results through sensitivity analyses and validated them using meta-analysis with AP and CP data from the UK Biobank in the GWAS catalog.

Results: A total of 36 immune traits showed significant associations with susceptibility of four types of pancreatitis, including AP (7 traits), AAP (8 traits), CP (14 traits), and ACP (7 traits). Twenty characteristics were found to be potential risk factors for pancreatitis, identified in B Cells (5 traits), conventional dendritic cells (cDCs, 2 traits), maturation stage of T cells (2 traits), monocytes (2 traits), myeloid cells (2 traits), T cells, B cells, natural killer cells (TBNK, 2 traits), and regulatory T cells (Treg cells, 5 traits). Multiple sensitivity analyses confirmed the validity of the findings. Meta-analysis confirmed a solid causal relationship between CX3CR1 on CD14^- CD16^-of monocyte panel and the susceptibility of CP.

Conclusions: Our MR study identified immune traits causally linked to acute and chronic pancreatitis, offering new insights for early clinical intervention and immune cell-targeted therapies.

Keywords: Causal association; Genome-wide association study; Immune traits; Mendelian randomization; pancreatitis.