Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014;39(1):77-82.
doi: 10.5114/ceji.2014.42129. Epub 2014 Apr 17.

Multiple gene mutations in patients with type 2 autoimmune pancreatitis and its clinical features

Feng Dong  1 , Qing-Quan Chen  2 , Ze-Hao Zhuang  3 , Qing-Liang He  4 , Feng-Qing Wang  5 , Qi-Cai Liu  5 , He-Kun Liu  6 , Yu Wang  7
Affiliations

Multiple gene mutations in patients with type 2 autoimmune pancreatitis and its clinical features

Feng Dong et al. Cent Eur J Immunol. 2014.

Abstract

Background: It is now clear that there are two histological types (type 1 and type 2) of autoimmune pancreatitis (AI P). The histological substance of type 1 AI P is known as lymphoplasmacytic sclerosing pancreatitis (LPSP) or traditional AIP, and type 2 AIP is characterized by distinct histology called idiopathic duct centric pancreatitis (IDCP). Serum IgG4 increase is considered as a marker for type 1 AI P. Far less is known about type 2 and it lacks predicting markers, so it easily leads to missed diagnosis and misdiagnosis.

The aim of this study: The aim of this study was to describe multi-gene mutations in patients with type 2 AI P and its clinical features.

Material and methods: Three unrelated patients with type 2 AI P, 10 cases with type 1 AIP, 15 cases with other chronic pancreatitis and 120 healthy individuals were studied. The mutations and polymorphisms of 6 genes involved in chronic pancreatitis or pancreatic cancer - PRSS1, SPINK1, CFTR, MEN1, PKHD1, and mitochondrial DNA - were sequenced. Information of clinical data was collected by personal interview using a structured questionnaire.

Results: Novel mutations were found in the genes encoding for MEN1 (p.546 Ala > The) and PKHD1 (c. 233586 A > G and c. 316713 C > T) from patients with type 2 AIP. What is more, the serum TCR (T cell receptor) level is relatively higher in patients with type 2 AIP than in patients with type 1 AIP and other chronic pancreatitis or normal controls. Weight loss was the major manifestation and no patients had extrapancreatic involvement in type 2 AIP.

Conclusions: Type 2 AIP may occur with multi-gene mutations. For screening purposes, it is more reasonable to evaluate TCR levels in serum.

Keywords: autoimmune pancreatitis; gene mutations; serum TCR; type 2.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Different serum TCR in type 2 AIP, type 1 AIP, chronic pancreatitis, and normal controls
Fig. 2
Fig. 2
Sequencing of gene mutations of patients with type 2 AIP. A) sequencing of mitochondrial m.A3243G mutation of blood sample of patients with type 2 AIP (No.1); B) sequencing of MEN1 gene mutation (p.546 Ala > The) of blood samples of patients with type 2 AIP(No.1, No.3); C and D) sequencing of PKHD1 gene silent mutation c. 233586 A > G (No. 1 and No. 2) and c. 316713 C > T (No. 2 and No. 3) of blood samples of patients with type 2 AIP
Fig. 3
Fig. 3
Histopathologic examination of the pancreas (magnification 400×). A) large number of inflammatory cell infiltrations (mainly neutrophils). B) IgG4 staining, positive plasma cells < 10%
See this image and copyright information in PMC

References

    1. Yoshida K, Toki F, Takeuchi T, et al. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 1995;40:1561–1568. - PubMed
    1. Uchida K, Okazaki K, Konishi Y, et al. Clinical analysis of autoimmunerelated pancreatitis. Am J Gastroenterol. 2000;95:2788–2794. - PubMed
    1. Kamisawa T, Funata N, Hayashi Y, et al. Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut. 2003;52:683–687. - PMC - PubMed
    1. Kamisawa T, Chari ST, Giday SA, et al. Clinical profile of autoimmune pancreatitis and its histological subtypes: an international multicenter survey. Pancreas. 2011;40:352–358. - PubMed
    1. Kamisawa T, Notohara K, Shimosegawa T. Two clinicopathologic subtypes of autoimmune pancreatitis: LPSP and IDCP. Gastroenterology. 2010;139:22–25. - PubMed

LinkOut - more resources