The Significance of FOXP3+Treg and IgG4 Expression in the Duodenal Papilla in Patients with Autoimmune Pancreatitis

Background: The expression of the forkhead/winged helix family of transcription factor P3 regulatory T cells (FOXP3+ Treg), a master gene of Treg, has recently been reported in autoimmune pancreatitis (AIP) patients, however, the local expression and clinical significance in biopsy specimens have not been elucidated. Aim: To evaluate the clinical significance of the expression of FOXP3+Treg in the main duodenal papilla in patients with AIP. Methods: Fourteen consecutive patients with AIP registered between April 2006 and October 2008 who underwent both ERCP and endoscopic biopsy were enrolled in this study. The endoscopic features and results of immunohistochemical examination of the duodenal papilla using FOXP3+ Treg, IgG4 antibodies with high-power fields (HPF) were reviewed. Immunohistopathological examination of resected AIP specimens (n=3) were also performed. The findings in the AIP patients were compared with those in 10 patients with papillitis, a tumor of the duodenal papilla (n=10). The numbers of FOXP3+ Treg and IgG4-positive plasma cells per high-power field were counted in all the histopathological specimens. To evaluate the effectiveness of corticosteroid therapy, we also studied the FOXP3+ Treg and IgG4 expression before and after the therapy. Results: A swollen main duodenal papilla was observed in 13 (13/14, 94%) patients with AIP and 3 (3/10, 30%) with papillitis (p<0.05). In resected AIP cases, the FOXP3+ Treg and IgG4 expression were well-recognized in the stroma of the pancreas. As for FOXP3+ Treg expression in duodenal papilla, it was 4.0±6.9/HPF in papillitis, 18.6 ± 9.0/HPF in AIP, and 27.8 ± 10.6/HPF in tumor specimens. The IgG4 expression was 0.9 ± 1.1/HPF in papillitis, 33.2 ± 19.8/HPF in AIP and 1.5 ± 1.9/HPF in tumors specimens. FOXP3+ Treg expression was more significantly recognized in AIP and duodenal tumor patients than in patients with papillitis (p < 0.05). IgG4 expression was also more significantly recognized in AIP patients than in papillitis or tumor patients (p < 0.05). The FOXP3+ Treg and IgG4 expression in AIP cases was reduced after corticosteroid therapy, however, the expression was still recognized in cases with recurrent AIP after the therapy. Conclusions: This prospective study showed that both FOXP3+Treg and IgG4 expression in the main duodenal papilla have a diagnostic value for AIP. We suggest that these findings may be valuable adjuncts to the diagnosis of AIP as well as for evaluating the effectiveness of corticosteroid therapy.