Sensitivity and Specificity of Serum IgG4 Levels for the Diagnosis of Autoimmune Pancreatitis

Abstract

Purpose: Serologic abnormalities are an important adjunct to diagnosis of AIP. Elevated levels of serum IgG4 have been reported to be highly sensitive and specific for AIP. These results have not been confirmed in Western populations. Aims: a) Assess the diagnostic accuracy of elevated levels of total IgG and IgG4 for AIP and the prevalence of elevated IgG4 levels in other pancreatic diseases, especially pancreatic cancer b) Compare the characteristics of patients with elevated IgG4 levels with and without AIP, as well as AIP patients with and without elevated IgG4 levels. Methods: We measured total IgG and IgG4 levels in 43 patients with AIP diagnosed by HISORt criteria and 457 consecutive patients attending the Pancreas Clinic with a final diagnosis of pancreatic cancer (N = 143), chronic pancreatitis (N = 77), acute pancreatitis (N = 58), benign pancreatic tumor (N = 62), miscellaneous pancreatic disorders (N = 57) and no pancreatic disease (N = 60). Results: For diagnosis of AIP, elevation of IgG4 levels had better sensitivity compared to total IgG (32/43 (74%) vs 16/43 (37%), p < 0.001). All 16 AIP patients with elevated total IgG also had IgG4 elevation. Among AIP patients, those with elevated IgG4 levels were more likely to be male compared to those with normal IgG4 levels (91% vs 55%, p= 0.007); age and proportion presenting with obstructive jaundice were similar. Among various non-AIP groups, the prevalence of elevated IgG4 levels was 3 to 10%; prevalence was similar among groups. When comparing patients with elevated IgG4 levels with and without AIP, non-AIP patients (“false positives”) were more likely to be female (45% vs 9%, p= 0.001), have a normal total IgG (84% vs 47%, p= 0.002) and have serum IgG4 levels less than 2 times the upper limit of normal (87% vs 31%, p < 0.001). Conclusions: Elevated serum IgG4 levels are characteristic of AIP and present in majority (74%) of patients. Even among subjects with wide variety of pancreatic diseases, elevated serum IgG4 levels are highly specific (93%) for AIP. However elevated IgG4 levels do occur in other pancreatic diseases including pancreatic cancer. Since AIP is a relatively rare disease, elevated IgG4 levels in subjects with low pretest probability of having AIP are likely to represent false positives.