Primary sclerosing cholangitis (PSC) is a syndrome of unknown etiology characterized by an association with inflammatory bowel disease in 50% or more cases. Since altered immunity, including circulating immune complexes, has been implicated in the pathogenesis of inflammatory bowel disease, we postulated that humoral immune mechanisms might also be important in the development of PSC. Therefore, as an initial step in testing this hypothesis, we examined sera of patients with PSC for the presence of circulating immune complexes by two independent methods: Clq binding and Raji cell assays. Twenty-four patients with PSC, 16 of whom had coexisting chronic ulcerative colitis, were prospectively selected by predefined biochemical, histologic, and radiographic criteria. Sixteen patients with inflammatory bowel disease and normal liver tests as well as six patients with extrahepatic biliary obstruction served as disease controls. Sera were positive for circulating immune complexes by at least one method in 80% (16/20) of patients with PSC; 70% (14/ 20) were positive by the Raji cell assay, 68% (14/24) by the Clq binding assay, and 45% (9/20) by both methods. Levels of circulating immune complexes by each assay were higher in sera from patients with PSC than in sera from healthy controls or patients with inflammatory bowel disease alone (p < 0.01). There were no differences in the levels of circulating immune complexes or in the frequency of positive tests in PSC patients with or without associated inflammatory bowel disease. In addition, there was no difference between the Raji cell binding of sera from six patients with extrahepatic biliary obstruction and six healthy controls tested concurrently. These data are consistent with the hypothesis that immunologic mechanisms may be important in the pathogenesis of PSC.
Primary sclerosing cholangitis (PSC) is a syndrome of unknown etiology characterized by inflammation and fibrosis of the intra-and extrahepatic bile ducts. The disease generally follows an unpredictable but slowly progressive course leading to biliary cirrhosis, portal hypertension, and death from liver failure (1).
PSC can occur alone or in association with inflammatory bowel disease (2), most commonly chronic ulcerative colitis. Recent data (1, 3) indicate that between one-half and three-quarters of all patients with PSC also have inflammatory bowel disease. Although the significance of this striking association is unclear, it could have patho-~-