Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Vol. 20; no. 1; pp. 74 - 78
• Main Authors: Mohapatra, Sonmoon, Charilaou, Paris, Sharma, Ayush, Singh, Dhruv Pratap, Sah, Raghuwansh P., Murray, David, Majumder, Shounak, Topazian, Mark D., Chari, Suresh T.
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.01.2020; Elsevier Limited
• Subjects: Age; Asthma; Autoimmune pancreatitis; Binding sites; Blood diseases; Diagnosis; Electronic medical records; Eosinophilia; Gender; IgG4-related disease; IgG4-related pancreatobiliary disease; Immunoglobulin G; Laboratories; Lymphoma; Medical diagnosis; Patients; Peripheral eosinophilia; Serum IgG4 level; IgG4-related pancreatobiliary disease; IgG4-related disease; Peripheral eosinophilia; Autoimmune pancreatitis; Serum IgG4 level
• DOI: 10.1016/j.pan.2019.11.016
• ISSN: 1424-3903; 1424-3911

In this study, we aim to assess the diagnostic utility of elevated serum IgG4 (sIgG4) concentration alone and in combination with peripheral eosinophilia (PE) for IgG4-related disease (IgG4-RD). From the Mayo Clinic, Rochester electronic medical record database we identified 409 patients with above normal levels of sIgG4 (reference range 121–140 mg/dL) who had sIgG4 measured to differentiate IgG4-RD from another disease. Among 409 patients with any elevation in sIgG4 levels, 129 (31.5%) had a definite diagnosis of IgG4-RD. The prevalence of PE increased with increasing sIgG4 levels and was more likely to be seen in subjects with IgG4-RD vs. non-IgG4-RD at ≥1X (n = 35/120, 29.2% vs. n = 23/258, 8.9%; p < 0.001), ≥2X (n = 23/64, 35.9% vs. n = 5/54,9.3%; p = 0.001) and ≥3X (n = 18/42, 42.9% vs. n = 0/9, 0%; p = 0.015) of sIgG4 upper limit of normal (ULN), respectively. After adjusting for gender and age, sIgG4 levels ≥ 2X ULN with PE as a predictor, had a higher positive predictive value in predicting IgG4-RD (72.2% vs. 65.9%) with an Area Under the Receiver Operatic Characteristic Curve (AUC) of 0.776, compared to sIgG4 ≥ 2X ULN without PE predictor (AUC = 0.74), p = 0.016. PE, sIgG4≥2X ULN, male gender, and age independently predicted the disease with odds ratio of 4.89 (95% CI:2.51–9.54), 3.78 (95% CI:2.27–6.28), 2.78 (95% CI:1.55–4.97), and 1.03 (95% CI:1.02–1.05), respectively. Even in subjects in whom IgG4-RD is suspected, only a minority (∼30%) with elevated sIgG4 levels have IgG4-RD. sIgG4 by itself is more specific at higher levels, though never diagnostic. PE increases with increasing sIgG4 and adds diagnostic value at higher sIgG4 levels.