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.
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Acknowledgments
The authors sincerely thank the participants for their help and willingness to take part in this study. The authors also thank Ms. Chen Jing for her help with the interpretation of data. This work was financially supported by the National Natural Science Foundation of China (no. 81571613, no. 81572442, no. 81201590, and no. 21275028) and a grant from the Natural Science Foundation of Fujian (no. 2013J01302) and a grant from Fujian Medical Innovations (no. 2012-CXB-21) and a grant from Outstanding Youth Foundation of Fujian High Education (no. JA12133) and by the National key Technology R&D Program of China (no. 2012AA022604).
Authors’ Contributions
Q.-C.L., F.G., and C.-D.W. planned the project. Q.-C.L., F.G., F.D., Z.-H.Z., and G.-Z.L. conceived and designed the study. F.G., Z.-H.Z., J.-T.C., and J.-F.P. performed the sample collection. S.C., Q.-Q.C., F.G., and S.-H.W. performed immunohistochemistry. Q.-C.L., F.G., and Q.-Q.C. participated in the in vivo procedures. Q.-C.L., F.G., and X.-H.L. performed the expression analysis. Q.-C.L., F.G., S.-H.W., L.-Q.L., and J.-T.C. analyzed the data and drafted the manuscript. All authors reviewed the manuscript and approved the final version.
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Liu, Qc., Dong, F., Pan, Jf. et al. Antibodies to Type IV Collagen Induce Type 1 Autoimmune Pancreatitis. Inflammation 39, 592–600 (2016). https://doi.org/10.1007/s10753-015-0284-0
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DOI: https://doi.org/10.1007/s10753-015-0284-0