The Spectrum of Sclerosing Cholangitis and the Relevance of IgG4 Elevations in Routine Practice

Abstract

SC is a heterogeneous liver injury. IgG4 testing may be clinically important in all patients, since it appears to identify a distinct patient population, more so than just those with AIP.

Primary Sclerosing Cholangitis

“…Around half of patients have raised IgM levels. Serum IgG4 levels are raised in 9-26% of patients with PSC, compared with only 1% of patients with another biliary disease, primary biliary cirrhosis [13,14,15,16]. It is important to test serum IgG4 levels in all patients with PSC, as elevated levels (>1.4 g/l) may confer a poorer prognosis [13,15].…”

Liver and the Biliary Tract

“…However, it should be noted that IgG4 serum levels are not entirely reliable, since they may be normal in 30-50% of cases and elevations of IgG4 serum levels can be seen in other diseases/malignancies (Webster et al, 2009), including in 10-20% of PSC patients (Alswat et al, 2012;Bjornsson et al, 2007), and elevated serum levels above 135-140 mg/dl are also seen in other liver diseases (including cirrhosis and malignancy). IgG4 levels also do not distinguish between IAC and CCA until the fourfold limit, which is much more specific to IAC (Oseini et al, 2011).…”

Primary Sclerosing Cholangitis: New Approaches to Diagnosis, Surveillance and Treatment

“…This higher cutoff level may be particularly justified when IgG4 serum levels are determined retrospectively in patients (previously) classified as PSC. Routine testing for IgG4 as recommended by recent guidelines for the management of PSC [9] may therefore identify a significant proportion of patients with IgG4 elevations and prospective studies are needed to clarify the best clinical approach for this subgroup of individuals [19]. Importantly, not all patients showing elevated serum IgG4 levels will have classic autoimmune pancreatitis or IAC, but some of them may potentially benefit from immunosuppression, irrespective of their formal disease classification [19].…”

“…About 10–20% of PSC patients test positive for elevated serum IgG4 (mean around 240 mg/dl, range: 216–357) and may even have IgG4-positive plasma cells in their liver explant tissue [17,19]. It is currently unclear whether such patients may represent (1) a subgroup of PSC with more rapid disease progression and more advanced disease, (2) an overlap syndrome of PSC with IAC or (3) could just be typical IAC which may have been misdiagnosed or misclassified as PSC.…”