title: Antibodies to Type IV Collagen Induce Type 1 Autoimmune Pancreatitis.
abstract: Type 1 autoimmune pancreatitis (AIP) is prototypic autoantibody-mediated diseases. Sclerosis accompanied by fiber deposition is generally regarded as the primary lesion in the development of obliterative vasculitis. However, why collagens or their antibodies play a crucial role in the pathogenesis of AIP has not been demonstrated. This study was performed to investigate if anti-collagen type IV antibodies (ACIVAbs) are the key factor of fiber deposition and recruit leukocytes, resulting in obliterative vasculitis in pancreas. Enzyme-linked immunosorbent analyses (ELISA) were used to measure the expression of Col IV and ACIVAbs in serum of patients with and without AIP. In vitro, adhesion and proliferation were determined by human lymphocytes incubated with Col IV and ACIVAbs. In vivo, C57BL0/6 mice were immunized with IgG-ACIVAbs, followed by analysis of clinical phenotype. IgG-ACIVAbs were recognized by the serum specimens from 12 of 22 patients with type 1 AIP, 3 of 9 patients with Crohn's disease, and 2 of 18 patients with pancreatic cancer, but not in healthy controls and acute pancreatitis. In patient's biopsy, ACIVAb staining increased and co-localized with subepithelial IgG4 deposits along the capillary walls and surrounding nerve fibers. In vitro, recombinant IgG-ACIVAbs increased leukocyte adhesion and proliferation. What is more, AIP could be induced in mice by immunization with IgG-ACIVAbs into adult mice.
authors.affiliation: Department of Laboratory Medicine, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
authors.forename: Qi-cai
authors.initials: QC
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Pharmacy, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Pan
authors.affiliation: Department of Gastroenterology, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
authors.forename: Ze-hao
authors.initials: ZH
authors.lastname: Zhuang
authors.affiliation: Department of Pathology, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.|Graduate Education College, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Surgery, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
authors.forename: Guo-zhong
authors.initials: GZ
authors.lastname: Liu
authors.affiliation: Medical Technology and Engineering College, Fujian Medical University, Fuzhou, 350005, China.
authors.forename: Qing-quan
authors.initials: QQ
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China.
authors.forename: Shao-huang
authors.initials: SH
authors.lastname: Weng
authors.affiliation: Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China.
authors.forename: Li-qing
authors.initials: LQ
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
authors.forename: Jin-tong
authors.initials: JT
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Medical Technology and Engineering College, Fujian Medical University, 88 Jiaotong Road, 350004, Fuzhou, China. cmjy503@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China. wangcdhl@sina.com.
authors.forename: Cheng-dan
authors.initials: CD
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China. linxinhua8798@163.com.
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002648:Child; D024141:Collagen Type IV / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology*; D010195:Pancreatitis / Q000276:immunology* / Q000473:pathology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D024141:Collagen Type IV; D007074:Immunoglobulin G
keywords: antibodies; autoimmune pancreatitis; collagen type IV; obliterative vasculitis