Blue-collar work is a risk factor for developing IgG4-related disease of the biliary tract and pancreas

BACKGROUND & AIMS: Immunoglobulin G4-related disease (IgG4-RD) of the biliary tract and pancreas is a fibroinflammatory disease of unknown origin with striking male predominance. We aimed to investigate whether blue-collar work and occupational contaminant exposure are risk factors for IgG4-RD of the biliary tract and pancreas. METHOD: We performed an age-/sex-matched case-control study in the largest academic medical centers of the Netherlands. Occupational history was surveyed by questionnaires. The International Standard Classification of Occupations (ISCO88) was used to classify jobs. Job exposure matrices ALOHA and DOM were utilized to assess the years individuals were exposed to compounds. The disease control cohort consisted of patients from 6 equally sized groups. Conditional logistic regression was used to assess effects of blue-collar work and exposure to occupational contaminants on developing IgG4-RD of the biliary tract and pancreas. RESULTS: Overall, 101 patients with IgG4-RD of the biliary tract and pancreas were matched 1:3 to 303 controls. Patients with IgG4-RD had a lower level of education (p = 0.001). Individuals who at least once performed blue-collar work (>1 year), had higher odds of developing IgG4-RD than individuals that only performed white-collar work (odds ratio [OR] 3.66; CI 2.18–6.13; p <0.0001). Being ever exposed (>1 year) to industrial ALOHA (e.g. mineral dust; vapors-dust-gases-fumes) and DOM compounds (e.g. asbestos) resulted in higher odds of IgG4-RD (OR 2.14; 95% CI 1.26–3.16; p <0.001 and OR 2.95; 95% CI 1.78-4.90; p <0.001, respectively). CONCLUSION: Blue-collar work is a risk factor for developing IgG4-RD of the biliary tract and pancreas putatively driven by exposure to selected industrial compounds; this may explain the striking male predominance among patients. LAY SUMMARY: Immunoglobulin G4-related disease (IgG4-RD) causes tumor-like lesions and typically affects middle-aged to elderly men. The background and cause of this disease remain relatively unknown. In this study, we identified blue-collar work as a risk factor for developing IgG4-RD of the biliary tract and pancreas, which may explain the striking male predominance among patients. Furthermore, these results suggest that toxic exposure to occupational contaminants may drive autoimmunity in IgG4-RD of the biliary tract and pancreas.