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

Abstract

Background: It is now clear that there are two histological types (type 1 and type 2) of autoimmune pancreatitis (AIP). The histological substance of type 1 AIP 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 AIP. 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 was to describe multi-gene mutations in patients with type 2 AIP and its clinical features. Material and methods: Three unrelated patients with type 2 AIP, 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.