Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis

OBJECTIVES: Biliary strictures, similar to primary sclerosing cholangitis (PSC), have been reported in patients with autoimmune pancreatitis, which is characterized by elevated serum IgG4 levels and responsiveness to corticosteroids. We sought to determine the frequency of elevated IgG4 in patients with PSC and to clinically compare PSC patients with elevated and normal IgG4 levels. METHODS: We measured serum IgG4 in 127 patients with PSC and 87 patients with primary biliary cirrhosis, as disease controls. Demographic, clinical, and laboratory characteristics were compared between the PSC groups with normal and elevated IgG4 (> 140 mg/dL). RESULTS: Elevated IgG4 was found in 12 PSC patients (9%) versus one PBC patient (1.1%) (p = 0.017). Patients with elevated IgG4 had higher total bilirubin (p = 0.009), alkaline phosphatase (p = 0.01), and PSC Mayo risk score (p = 0.038), and lower frequency of IBD (p < 0.0001). Importantly, the time to liver transplantation was shorter in patients with elevated IgG4 (1.7 vs 6.5 yr, p = 0.0009). The type of biliary involvement (intrahepatic, extrahepatic, or both) and pancreatic involvement were similar in both groups. CONCLUSIONS: A small proportion of PSC patients had elevated serum IgG4. In these patients parameters of liver disease severity were more pronounced and time to liver transplantation was shorter, suggesting a more severe disease course. It is possible that this subset of patients behaves similarly to autoimmune pancreatitis patients with biliary strictures, and could potentially respond to corticosteroids. Testing PSC patients for IgG4 and treating those with elevated levels with corticosteroids in clinical trials should be considered.