Implications of Serum IgG4 Levels for Pancreatobiliary Disorders and Cancer

Background/Objectives: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated disorder presenting as mass-like lesions with obstructions. An elevated serum IgG4 level is identified in more than half of affected patients and is considered a diagnostic criterion. IgG4-RD is still easily misdiagnosed as neoplastic or infectious disease. We aimed to conduct a hospital-based study to illuminate the association between serum IgG4 levels and pancreatobiliary disorders and cancer. Methods: In this study, serum IgG4 levels were assessed at our hospital's immunology laboratory, utilizing data from the hospital's computer center, and the diagnostic codes used were based on ICD-9-CM. We analyzed IgG4 level data collected between April 2013 and April 2020, including patients' age, gender, and diseases, but excluding the rationale for IgG4 level assessment. Employing propensity score matching (PSM) at a 1:1 ratio to mitigate age and gender confounding, we analyzed 759 patients divided into groups by IgG4 levels (≤140 and >140 mg/dL; and ≤140, 141-280, >280 mg/dL). We explored associations between IgG4 levels and conditions such as pancreatobiliary cancer (the group included cholangiocarcinoma, pancreatic cancer, and ampullary cancer), cholangitis, cholangiocarcinoma, pancreatitis, pancreatic cancer, and ampullary cancer. Results: Our study analyzed the demographics, characteristics, and serum IgG4 levels of participants and found no significant differences in serum IgG4 levels across various pancreatobiliary conditions. Nevertheless, the crude odds ratios (ORs) suggested a nuanced association between a higher IgG4 level > 280 mg/dL and increased risks of cancer and pancreatitis, with crude ORs of 1.52 (p = 0.03) and 1.49 (p = 0.008), respectively. After PSM matching, the further analysis of 759 matched patients showed no significant differences in IgG4 levels > 140 mg/dL between cancerous and non-cancerous groups, nor across other pancreatobiliary conditions. A higher serum IgG4 level > 280 mg/dL was significantly associated with pancreatobiliary cancer and cholangiocarcinoma, with crude ORs of 1.61 (p = 0.026) and 1.62 (p = 0.044), respectively. In addition, IgG4 > 280 mg/dL showed a greater association with pancreatic cancer compared with 141-280 mg/dL, with crude OR of 2.18 (p = 0.038). Conclusions: Our study did not find a clear association between serum IgG4 levels (>140 mg/dL) and pancreatobiliary cancer. We observed that higher IgG4 levels (>280 mg/dL) may be associated with cholangiocarcinoma and pancreatic cancer, as indicated by crude ORs. However, the adjusted analysis did not demonstrate the significant association between IgG4 level > 280 mg/dL and cancer. Considering IgG4-RD as a chronic and persistent inflammatory status, it is more closely associated with inflammatory diseases than with cancer. Therefore, further long-term cohort studies are necessary to evaluate the potential role of IgG4 levels in cancer risk among these patients.