IgG4+ Plasma Cell Infiltrates in Liver Explants with Primary Sclerosing Cholangitis
L Zhang, J Lewis, SC Abraham, S Leung, C Rosen, J Poterrucha, TT Wu. Mayo Clinic, Rochester; MD Anderson Cancer Center, Houston
Background: Sclerosing cholangitis can be primary (PSC) or secondary. One unusual cause of secondary sclersoing cholangitis is the newly-recognized entity of IgG4-related sclerosing disease. The prevalence and significance of IgG4+ plasma cells in patients who are clinically and radiologically classified as PSC, however, are unknown.
Design: We studied 99 consecutive liver transplants performed for clinical/radiologic diagnoses of PSC between 1996-2005. Periductal lymphoplasmacytic infiltrates in the explanted livers were scored as none, mild, moderate, or marked, and sections with the most prominent infiltrates were chosen for IgG4 immunohistochemistry (1:100; Zymed/Invitrogen). Corresponding cholecystectomy specimens (avavilable in 74 cases) were also subjected to IgG4 immunostaining. IgG4 positivity (defined as >10 IgG4+ plasma cells/high power field) was correlated with clinical features (age, gender, presence of inflammatory bowel disease, PSC duration, PSC recurrence after transplant, and number of acute rejection episodes) and histologic findings in the liver explants (periductal fibrosis and degree of periductal lymphoplasmacytic inflammation).
Results: Twenty-three (23.2%) liver explants showed increased (>10/HPF) IgG4+ periductal plasma cell infiltration. Histologically, IgG4 positivity in the liver strongly correlated with moderate to marked periductal lymphoplasmacytic inflammation (p=0.007) but only loosely with the presence of increased IgG4+ plasma cells in the gallbladder (17.6% vs 5.3%, p=0.13). All cases showed dense periductal fibrosis; there was no storiform fibrosis (as often seen in IgG4-associated pancreatitis). Clinically, IgG4 positivity correlated with shorter PSC duration before transplant (5.3 4.6 yrs vs 8.5 6.2 yrs, p=0.03), but was not associated with age, gender, IBD, PSC recurrence, or rejection.
Conclusions: Nearly one quarter of explanted livers that carry a clinical diagnosis of PSC contain increased IgG4+ periductal plasma cells, a finding that correlates with more intense periductal inflammation. Whether these patients also have increased serum IgG4 levels and whether this is a distinct subtype of PSC or represents an early (more inflammatory phase) of ordinary PSC are questions that require further study. The shorter time to liver transplant in these patients could suggest either a more aggressive disease course of untreated IgG4+ sclerosing cholangitis, or simply an earlier phase of PSC.
Category: Liver & Pancreas
Monday, March 9, 2009 2:30 PM
Platform Session: Section E, Monday Afternoon