Immunohistochemical differences in the portal tract and acinar infiltrates between primary biliary cirrhosis and autoimmune cholangitis

Background Antimitochondrial anti body-negative primary biliary cirrhosis, or autoimmune cholangitis, may be indistinguishable clinically and histologically from antimitochondrial anti body-positive primary biliary cirrhosis. Aims We aimed to compare the phenotypic markers of the portal and acinar infiltrates in autoimmune cholangitis and antimitochondrial antibody-positive primary biliary cirrhosis. Patients and methods Formalin-fixed, paraffin-embedded liver sections were identified from 32 patients with a clinical and histological diagnosis of primary biliary cirrhosis. Thirteen were antimitochondrial antibody-negative (autoimmune cholangitis group) and 19 were antimitochondrial antibody-positive. The groups were well matched for age, histological stage, liver biochemistry and drug treatment. Immunohistochemical staining was performed using monoclonal antibodies against CD3 (pan T cell), CD8 (cytotoxic), CD45RO (memory), CD45RA (naive), CD68 (macrophages) and against the secreted form of eosinophilic cationic protein (EG2). Results In autoimmune cholangitis, both portal and acinar CD3 cell counts were significantly higher than in antimitochondrial antibody-positive primary biliary cirrhosis (median portal count 421 vs 257 cells/graticule, P < 0.03; median acinar count 18 Its 9 cells/graticule, P < 0.02). There were no differences between the groups in portal or lobular CD8, CD45RO, CD45RA, CD68 or EG2. Of the total group (antimitochondrial antibody positives and negatives), there were significantly more CD45RA cells in early (stage 1) compared with cirrhotic (stage 4) disease (median 19.3 vs 14 cells/graticule, P < 0.03). EG2 staining was found in eight of the 32 sections overall, but not in the patients with stage 1 disease (P < 0.04). Conclusion CD3 counts are higher in autoimmune cholangitis than in antimitochondrial anti body-positive primary biliary cirrhosis in both portal and acinar areas. However, there are no significant differences in memory/naive T-cell subsets between both conditions and, in both, loss of naive T lymphocytes and secretion of eosinophilic cationic protein occur with disease progression. This implies that the effector pathways of bile duct destruction are similar in autoimmune cholangitis and primary biliary cirrhosis.