Foxp3 and IgG4 Expression in Subtypes of Autoimmune Pancreatitis
RV Mandal, K Notohara, V Deshpande, AB Farris, M Lisovsky, TC Smyrk, GY Lauwers, M Mino-Kenudson. Massachusetts General Hospital, Boston, MA; Kurashiki Central Hospital, Kurashiki, Japan; Mayo Clinic, Rochester, MN
Background: Autoimmune pancreatitis (AIP) is probably a heterogenous category, including lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic ductocentric chronic pancreatitis (IDCP). LPSP appears to represent the pancreatic manifestation of systemic IgG4-related fibrosclerosing disease; however, the nature of IDCP has not been well studied. Forkhead box P3 (Foxp3) is a specific transcription factor expressed by CD4+CD25+ regulatory T cells (Tregs). Large numbers of Foxp3+ Tregs have been found in organs involved by systemic IgG4-related fibrosclerosing disease and it is hypothesized that Tregs might be involved in IgG4 class switching and fibroplasia. The aim of this study was to evaluate and compare Foxp3 and IgG4 expression between LPSP and IDCP.
Design: Surgically resected LPSP (n=22) and IDCP (n=13) cases were evaluated for several pathologic features characteristic of AIP including: the extent of inflammation, inflammatory pseudotumor-like changes, and obliterative phlebitis. Foxp3, IgG4, and IgG1 immunostains were performed and an average number of Foxp3+ Tregs/HPF and an IgG4+ plasma cell/IgG1+ plasma cell ratio (IgG4/IgG1) were compared between the LPSP and IDCP cases and were correlated with the histologic parameters.
Results: Large numbers of Foxp3+ Tregs were found in both LPSP and IDCP cases (mean: 49.6/HPF vs. 37.3/HPF, respectively, p=0.12). The mean IgG4/IgG1 was higher in the LPSP group than in the IDCP group (1.23 vs. 0.31, respectively, p < 0.001). The numbers of Tregs correlated with IgG4/IgG1 in the LPSP group (p=0.025), but no such correlation was observed in the IDCP or entire cohort. There was no significant difference in any of histologic parameters between cases with > 40 Tregs/HPF and those with < 40 Tregs/HPF in the LPSP, IDCP or entire cohort. Conversely, a higher IgG4/IgG1 (> 0.50) was associated with dense lymphoplasmacytic infiltration in lobules (p=0.023), extensive obliterative phlebitis (p=0.004), and a larger caliber of obliterated veins (p < 0.001) in the entire cohort.
Conclusions: The increase in Tregs is associated with a high IgG4/IgG1 ratio in LPSP, but not in IDCP. The results support the hypothesis that Tregs might be involved in IgG4 class switching in LPSP that is, in turn, associated with characteristic histologic features. The large number of Tregs seen in IDCP may simply represent immune reactions to various stimuli such as infection.
Category: Liver & Pancreas
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 221, Wednesday Morning