Diagnostic utility of IgG and IgM immunohistochemistry in autoimmune liver disease

Abstract

Aim: To assess the role of IgM and IgG immunohistochemistry (IHC) in the evaluation of autoimmune liver conditions--autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC).

Methods: Forty one biopsies from untreated patients diagnosed with autoimmune liver disease (AIH, n = 20; PBC, n = 13; PSC, n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected. IgM and IgG-positive plasma cells were counted in each sample.

Results: A predominance of IgG-positive plasma cells was seen in AIH (90% of cases), PSC (75% of cases), and chronic hepatitis C (100% of cases), while IgM-positive plasma cells predominated in PBC (92.8% of cases). The IgM /IgG ratio (< 1 or > or = 1) accurately distinguished PBC from AIH in 90.9% of cases (sensitivity = 92.3%, specificity = 90%), and PBC from either AIH or PSC in 87.8% of cases (sensitivity = 92.3%, specificity = 85.7%).

Conclusion: Plasmacytic infiltrates expressing predominantly IgM are characteristic of PBC, while other forms of liver disease analyzed in this study, including AIH, typically show an IgG-predominant plasma cell infiltrate. Our data indicate that IgM and IgG IHC may be a useful tool when PBC is a diagnostic consideration.

Figure 1

Immunoglobulin expression in autoimmune hepatitis and primary biliary cirrhosis. IgG-positive plasma cells (A) outnumber IgM-positive plasma cells (B) in most cases of autoimmune hepatitis (AIH); In contrast, IgM-positive plasma (C) cells predominate over IgG-positive cells (D) in the majority of cases of primary biliary cirrhosis (PBC). IgG background staining within sinusoids and blood vessels is common due to the presence of serum IgG. (Immunohistochemistry, 400 × magnification).

Figure 2

IgM/IgG ratio distinguishes the majority of cases of primary biliary cirrhosis (IgM/IgG ratio ≥ 1) from all other groups (IgM/IgG ratio < 1). Single outlier in the AIH group was diagnosed with AIH-PBC sequential syndrome based on subsequent serology and pathological data (see discussion). Abbreviations: PBC: Primary biliary cirrhosis; AIH: Autoimmune hepatitis; PSC: Primary sclerosing cholangitis; CHC: Chronic hepatitis C.