CALCB splice region pathogenic variants leading to plasma cell neurotropic enrichment in type 1 autoimmune pancreatitis

Recently, we have demonstrated that PRSS1 mutations cause ectopic trypsinogen activation and thereby result in type 1 autoimmune pancreatitis (AIP). However, the molecules involved in inducing obliterative vasculitis and perineural inflammation in the pancreas are not well-described. The present stu...

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Bibliographic Details
Published in:Cell death & disease 2017-02, Vol.8 (2), p.e2591-e2591
Main Authors: Liu, Qi-cai, Chen, Falin, Wu, Chao-yang, Gao, Feng, Zhuang, Ze-hao, Chen, Jin-tong, Cai, Bin, Zhang, Tianming, Guo, Ling, Lin, Li-qing, Zhao, Cheng-fei, Lin, Xin-hua
Format: Article
Language:English
Subjects:
38/23
38/44
38/91
631/208/726/649
631/208/737
692/4020/1503/1712/1714/2755
692/420/2489
Antibodies
Autoimmune Diseases - genetics
Autoimmune Diseases - pathology
Biochemistry
Biomedical and Life Sciences
Calcitonin Gene-Related Peptide - genetics
Cell Biology
Cell Culture
Cell Line
Endoplasmic Reticulum - genetics
Female
Golgi Apparatus - genetics
HEK293 Cells
Humans
Immunology
Inflammation - genetics
Inflammation - pathology
Life Sciences
Male
MAP Kinase Signaling System - genetics
Mutation
Mutation - genetics
Original
original-article
Pancreas
Pancreas - pathology
Pancreatitis - genetics
Pancreatitis - pathology
Pathogens
Phosphorylation - genetics
Plasma
Plasma Cells - pathology
Trypsin - genetics
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Summary:Recently, we have demonstrated that PRSS1 mutations cause ectopic trypsinogen activation and thereby result in type 1 autoimmune pancreatitis (AIP). However, the molecules involved in inducing obliterative vasculitis and perineural inflammation in the pancreas are not well-described. The present study applied whole-exome sequencing (WES) to determine the underlying etiology and revealed novel missense splice region variants, CALCB c.88T>C (p.Ser30Pro) and IR [1]-mutants, in 2 of the 3 families and 2 of 26 unrelated patients with type 1 AIP. In vitro , both of the mutants displayed decreased βCGRP, ERK1/2 phosphorylation, and co-localized with endoplasmic reticulum and Golgi apparatus. The novel pathogenic variant identified in this case should contribute to our understanding of the expanding spectrum of AIP.
ISSN:2041-4889
2041-4889
DOI:10.1038/cddis.2017.32