Autoimmune pancreatitis (AIP), a major manifestation of immunoglobulin G4-related disease (IgG4-RD), is an immune-mediated disorder, but the target autoantigens are still unknown. We previously reported that IgG in patients with AIP induces pancreatic injuries in mice by binding the extracellular matrix (ECM). In the current study, we identified an autoantibody against laminin 511-E8, a truncated laminin 511, one of the ECM proteins, in patients with AIP. Anti-laminin 511-E8 IgG was present in 26 of 51 AIP patients (51.0%), but only in 2 of 122 controls (1.6%), by enzyme-linked immunosorbent assay. Because truncated forms of other laminin family members in other organs have been reported, we confirmed that truncated forms of laminin 511 also exist in human and mouse pancreas. Histologic studies with patient pancreatic tissues showed colocalization of patient IgG and laminin 511. Immunization of mice with human laminin 511-E8 induced antibodies and pancreatic injury, fulfilling the pathologic criteria for human AIP. Four of 25 AIP patients without laminin 511-E8 antibodies had antibodies against integrin α6β1, a laminin 511 ligand. AIP patients with laminin 511-E8 antibodies exhibited distinctive clinical features, as the frequencies of malignancies or allergic diseases were significantly lower in patients with laminin 511-E8 antibodies than in those without. The discovery of these autoantibodies should aid in the understanding of AIP pathophysiology and possibly improve the diagnosis of AIP.

IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice.

Integrin αvβ6 Colonic epithelial cells Connective tissues RGD RGD binding siteAnti-integrin αvβ6 autoantibodies in UC patients RGD

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Both ulcerative colitis and Takayasu's arteritis are thought to be organ-specific immunemediated inflammatory diseases. Wepresent the rare case of a 23-year-old womanwith a 4-year history of ulcerative colitis who developed Takayasu's arteritis one month after giving birth. She was found to carry the human leukocyte antigens (HLA)-B52 and DR2, which were previously noted to be associated with these inflammatory conditions in the Japanese population. The pathogenic relevance of this haplotype to the concomitant development of these two conditions is discussed. (Internal Medicine 35: 574-578, 1996)