Diagnostic Utility of Immunoglobulin Subclasses in Autoimmune Liver Diseases
RK Moreira, MK Washington. Vanderbilt University, Nashville, TN
Background: Plasma cells are seen in autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). Previous studies have shown that assessment of immunoglobulin subclasses in plasma cells by immunohistochemistry (IHC) may be useful in distinguishing PBC from AIH. Limited data exists regarding the immunophenotype of plasma cells in PSC . The prevalence and significance of IgG4-positive cells in autoimmune liver diseases has not been well studied. We investigate the role of IgM and IgG IHC in the differential diagnosis of autoimmune liver diseases on liver biopsies, and the prevalence and significance of IgG4-positive cells.
Design: Fifty biopsies from untreated patients diagnosed with autoimmune liver disease at our institution from 1993 to 2006 were selected. IHC for IgM, IgG (Cell Marque, 1:20.000), and IgG4 (Zymed, 1:800) were performed and the concentration of positive plasma cells (per mm2) was assessed.
Results: 21 patients with AIH (8 males (M), 13 females (F), mean age 32, range 4-63), 15 patients with PBC (1 M, 14 F, mean age 53, range 43-71), and 14 patients with PSC (9 M, 6 F, mean age 31, range 7-67) were included. A predominance of IgG-positive plasma cells is seen in AIH (90% of cases) and PSC (75% of cases), while IgM-positive plasma cells predominate in PBC (92.8% of cases). The IgM /IgG ratio (<1 or >=1) accurately distinguishes PBC from AIH in 91.4% of cases, and PBC from either AIH or PSC in 87.5% of cases (PPV=76.4%; NPV=95.6%). However, considerable overlap exists between PSC and either PBC and AIH by this method. The total number of plasma cells in AIH (mean=9.75 cells/mm2) tends to be higher than in PBC or PSC (mean=6.19 and 5.16 cells/mm2, respectively, p<0.05). Significant numbers of IgG4-positive plasma cells were seen in 28% of AIH cases, but only rare positive cells in PBC and PSC cases. IgG4-positive AIH cases were more likely to present with advanced fibrosis compared to IgG4-negative cases (66.6% vs 30%). No association was found with other IgG4-related conditions, presence of autoimmune diseases, response to steroids, or severity of inflammation on liver biopsy.
Conclusions: PBC and AIH can reliably be distinguished on initial biopsy by their IgM/IgG immunophenotype, while significant overlap exists between the latter two conditions and PSC. Our data indicates that IgM and IgG IHC may be a useful tool in evaluating autoimmune liver disease. A subset of AIH cases shows positive IgG4 cells, which may be a marker of more aggressive disease.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 150, Tuesday Morning