血清免疫球蛋白G4用於區分自體免疫胰臟炎和胰臟癌

Use of serum level of immunoglobulin G4 in the differential diagnosis of autoimmune pancreatitis and pancreatic cancer

背景：分析血清免疫球蛋白G4（IgG4）用於診斷自體免疫胰臟炎及區分自體免疫胰臟炎和胰臟癌的敏感度、特異度、陽性預測值、陰性預測值、陽性概似比以及陰性概似比。方法：我們收集865位於長庚醫院曾因懷疑自體免疫胰臟炎而有接受IgG4檢驗的病患，做回顧性分析。結果：血清IgG4中位數數值在自體免疫胰臟炎明顯高於其它胰臟問題病患（442mg/dL vs 73.8mg/dL，p值<0.001）。根據ROC曲線分析，用132mg/dL為切點區分自體免疫胰臟炎和胰臟癌，其敏感度為94.7%，特異度為78.8%，陽性預測值為63.5%，陰性預測值為97.5%，陽性概似比為4.46，以及陰性概似比為0.09。用兩倍正常值264mg/dL的IgG4數值為切點診斷自體免疫胰臟炎，陽性預測值提升至86.5%，陽性概似比可以提升至16.47。結論：血清IgG4數值在自體免疫胰臟炎明顯高於其它胰臟相關疾病。兩倍IgG4數值，不能完全排除胰臟癌，但可以高度懷疑為自體免疫胰臟炎。在非自體免疫胰臟炎的情形，仍可以見到有一定比例的病患血清IgG4升高。在胰臟癌有16.4%的比例出現輕微升高的IgG4數值情形（介於1~2倍正常值），因而容易出現假陽性。因此，我們認為兩倍的IgG4數值，可以排除大部份的假陽性，高的陽性預測值和高的陽性概似比，可以有較好的表現用於區分自體免疫胰臟炎和胰臟癌。

Background: To determine the diagnostic performance of elevated serum Immunoglobulin G4 (IgG4) in the diagnosis of autoimmune pancreatitis (AIP) and its ability to distinguish AIP from pancreatic cancer. Methods: We retrospectively analyzed serum IgG4 levels in 865 patients with suspected AIP. There were 57 patients with confirmed AIP, 146 with pancreatic cancer, 9 with idiopathic pancreatitis, 104 with acute pancreatitis, 106 with chronic pancreatic disease, and 443 with other pancreatic conditions, including benign enlargement of pancreas, abdominal pain, or obstructive jaundice. Results: The median serum IgG4 level was significantly greater in AIP patients than in patients with other pancreatic diseases (442.0 vs. 73.8 mg/dL, p<0.001). Based on an IgG4 cutoff value of 132 mg/dL (determined by receiver operating curve analysis), the sensitivity, specificity, and positive predictive values in the differential diagnosis of AIP and pancreatic cancer were 94.7%, 78.8%, and 63.5% respectively. Use of an IgG4 cutoff of 132 mg/dL meant that 31 of 146 patients (21.2%) with pancreatic cancer had elevated serum IgG4, 3 of 57 patients with AIP (5.2%) did not have elevated serum IgG4, and the positive and negative predictive values for diagnosis of AIP were 63.5% and 97.5% respectively. Conclusion: Serum IgG4 concentrations were significantly greater in AIP patients than in patients with other pancreatic diseases. A serum concentration of IgG4 that is more than 2 times the upper limit of normal is highly suggestive of AIP, but does not totally rule out pancreatic cancer. Mild (<2-fold) elevations in serum IgG4 were present in many subjects without AIP, including 16.4% of subjects with pancreatic cancer. IgG4 elevation in a patient with a low pretest probability of having AIP is likely to represent a false positive. However, the high predictive value and high positive likelihood ratio confirm the good performance of 2-fold cutoff value in the differential diagnosis of AIP and pancreatic cancer.