Objectives: Although recent reports demonstrate that eosinophilia is a distinctive feature of early stage primary biliary cirrhosis (PBC), the pathogenesis of this eosinophilia remains unknown. Clinical and experimental data suggest potential mast cell activation in cholestatic liver diseases. Because mast cell-derived mediators could induce eosinophil chemotaxis and activation, we hypothesized that mast cell activation may play a role in the pathogenesis of eosinophilia in PBC. Thus, as the first step in examining a possible link between mast cell activation and eosinophilia in PBC, we quantified the infiltration of mast cells and eosinophils in the livers of patients with PBC.
Methods: The study population consisted of 11 patients with stage I or stage II PBC and 11 patients with chronic viral hepatitis. Mast cells and eosinophils were identified by immunohistochemistry using monoclonal antibodies against mast cell tryptase (AA1) and eosinophilic cationic protein (EG2), respectively. Cell infiltration in the portal tract was quantitated morphometrically.
Results: When compared with patients with chronic viral hepatitis, patients with PBC showed significantly increased portal infiltration with mast cells (140 +/- 25 vs 72 +/- 10 cells/mm2 [mean +/- SEM, p < 0.05]) and eosinophils (76 +/- 19 vs 32 +/- 9 cells/mm2 [p < 0.05]). Numbers of portal mast cells correlated with numbers of eosinophils in patients with PBC (r = 0.60, p < 0.05) but not in patients with chronic hepatitis (r = 0.34, p = 0.47).
Conclusion: Concomitant increases in mast cell and eosinophil infiltration in the portal tract suggest a role for mast cell activation in the pathogenesis of eosinophilia in PBC.