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PRSS1_p.Leu81Met mutation results in autoimmune pancreatitis
Feng Gao, Yue-Ming Li, Guo-Lin Hong, Zhi-Feng Xu, Qi-Cai Liu, Qing-Liang He, Li-Qing Lin, Shao-Huang Weng
Feng Gao, Department of Pathology, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Yue-Ming Li, Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Guo-Lin Hong, Department of Laboratory Medicine, the Second Hospital of Fuzhou, Fuzhou 350007, Fujian Province, China
Zhi-Feng Xu, Department of Surgery, the 95 Hospital of PLA, Putian 351100, Fujian Province, China
Qi-Cai Liu, Department of Laboratory Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Qi-Cai Liu, Department of Laboratory Medicine, Medical Technology and Engineering College of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Qing-Liang He, Department of Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Li-Qing Lin, Shao-Huang Weng, Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou 350005, Fujian Province, China
Author contributions: Gao F and Li YM contributed equally to this work; Li YM, Hong GL and Liu QC defined the research theme; Gao F and Xu ZF designed methods and experiments, carried out the laboratory experiments, analyzed the data, interpreted the results and wrote the paper; He QL and Lin LQ co-designed the dispersal and colonization experiments, and co-worked on data collection and interpretation; Weng SH co-designed experiments and discussed analyses, interpretation, and presentation; all authors have read and approved the manuscript to be published.
Supported by National Natural Science Foundation of China, No. 81201362, No. 81201590, No. 21275028; Putian Municipal Science and Technology Bureau Project, No. 2009S3-3; Fujian Medical Innovations, No. 2012-CXB-21; Education Department of Fujian Province, No. JA12133, No. JA12143; National High Technology Investigation Project Foundation of China, No. 2012AA022604
Correspondence to: Qi-Cai Liu, MD, Department of Laboratory Medicine, the First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, Fujian Province, China. lqc673673673@163.com
Telephone: +86-591-87981972 Fax: +86-591-2263520
Received: December 13, 2012
Revised: February 18, 2013
Accepted: March 6, 2013
Published online: June 7, 2013
AIM: To describe protease serine 1 (PRSS1) gene mutations in patients with autoimmune pancreatitis (AIP) and the clinical features of AIP.
METHODS: Fourteen patients with AIP, 56 with other chronic pancreatitis, 254 with pancreatic cancer and 120 normal controls were studied. The mutations and polymorphisms of four genes involved with pancreatitis or pancreatic cancer, PRSS1, SPINK1, CFTR and MEN1, were sequenced. The pathogenic mechanism of AIP was investigated by comparing the wild-type expression system with the p.81Leu→Met mutant expression system.
RESULTS: Two novel mutations (p.81Leu→Met and p.91Ala→Ala) were found in PRSS1 gene from four patients with AIP. PRSS1_p.81Leu→Met mutation led to a trypsin display reduction (76.2%) combined with phenyl agarose (Ca2+ induced failure). Moreover, the ratio of trypsin/amylase in patients with AIP was higher than in the patients with pancreatic cancer and other pancreatitis. A large number of lymphocytes and plasma cells were found in the bile ducts accompanied by hyperplasia of myofibroblasts.
CONCLUSION: Autoimmune pancreatitis may be related to PRSS1 gene mutations.
Core tip: Novel mutations (p.81Leu→Met and p.91Ala→Ala) were found in protease serine 1 gene from the patients with autoimmune pancreatitis. Trypsinogen abnormal activation resulted in multiple organ injuries. And this offers direct evidence in support of the trypsinogen gene mutation and abnormal immune system.
