Role of immunologic costimulatory factors in the pathogenesis of biliary atresia.

BACKGROUND The authors studied the patterns of expression of immunologic costimulatory molecules (B7-1, B7-2, and CD40) in biliary atresia (BA) patients to confirm any correlation with clinical course/outcome. METHODS Based on clinical status 2 years postoperatively, 24 BA patients were divided into group I (n = 8, normal liver function), group II (n = 10, anicteric with moderate liver dysfunction), and group III (n = 6, icteric with severe liver dysfunction). Liver biopsies obtained at portoenterostomy and from 6 age-matched controls, were analyzed immunohistochemically using antibodies against B7-1, B7-2, and CD40. RESULTS There was no expression of B7-1, B7-2, or CD40 in any control liver specimen. In all BA specimens, B7-1, B7-2, and CD40 were expressed strongly in bile ductules in portal tracts. In groups with liver dysfunction, B7-1, B7-2, and CD40 were expressed strongly on the surfaces of Kupffer and dendritic cells and in hepatocyte cytoplasm. Positive staining cells were significantly fewer in patients with better clinical outcome. B7-1 was found in vascular and sinusoidal endothelial cells only in cases of postoperative portal hypertension. CONCLUSIONS Costimulatory factors expressed on bile ductules, hepatocytes, and vascular endothelial cells appear to mediate autoimmune processes causing progressive liver fibrosis and portal hypertension in BA.