Background: Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition with multisystem involvement. Given the heterogeneity of clinical presentations and the limitations of tissue biopsy, there is a growing need for reliable, non-invasive biomarkers. Serum IgG4 has emerged as a valuable serological marker, but its diagnostic precision is limited by considerable variability. Objective: To establish normative reference ranges for serum IgG4 in healthy adult North Indian males and propose diagnostic thresholds for IgG4-RD. Methods: This single-centre, observational study enrolled 203 healthy North Indian males (aged 20–60) to establish age-stratified normative IgG4 intervals by nephelometry. Retrospective analysis of 20 biopsy-confirmed IgG4-RD cases enabled assessment of diagnostic performance and determination of optimal serum IgG4 cutoffs. Results: The mean serum IgG4 concentration in healthy individuals was 767.1±462.7mg/L, with a median of 678mg/L and an IQR of 411.0–1031.8 mg/L. Median IgG4 values ranged from 569 to 806mg/L, with no age-related trend. In contrast, patients with IgG4-RD had a significantly higher mean IgG4 concentration of 5,518.4±7,205mg/L ( P = .01). ROC curve analysis demonstrated an AUC of 0.693 with 95% confidence interval CI: (0.56–0.83), highlighting only ‘moderate’ diagnostic accuracy. At a cutoff of 1262mg/L, serum IgG4 had a sensitivity of 70% and specificity of 58% for identifying IgG4-RD. Conclusion: Serum IgG4 levels exhibit wide interindividual variability but minimal age-related trends. A diagnostic threshold of 1262mg/L offers moderate accuracy for identifying IgG4-RD. These normative reference intervals enhance the diagnostic utility of serum IgG4 in clinical practice.
Singh et al. (Thu,) studied this question.