Serum IgG4 levels outperform IgG4/IgG RNA ratio in differential diagnosis of IgG4-related disease

IgG4-related disease (IgG4-RD) is a chronic inflammatory-fibrosing disorder affecting virtually any organ, but most frequently the pancreaticobiliary system. Differential diagnosis is challenging due to a highly variable clinical presentation and relies on multiple diagnostic criteria rather than on single markers. Previously, qPCR-based measurements of the IgG4/IgG mRNA ratio that originate from dominant IgG4⁺ B-cell receptor (BCR) clones have been propagated as a critical endeavor to fill this diagnostic gap. In the current study, we demonstrated in concordance with de Vires et al. on independent cohorts and with different methodological setups that IgG4/IgG mRNA ratio is prone to false-positive results, which could cause misdiagnosis of pancreaticobiliary cancer. Furthermore, we found superior test accuracy of serum IgG4 levels, likewise not a perfect biomarker itself. Therefore, our study questions the clinical benefit of IgG4/IgG mRNA ratios in the differential diagnosis of IgG4-RD in support of de Vires et al. but concurrently underpins the necessity for more reliable biomarkers to differentially diagnose IgG4-RD.

Publication History

Article published online:
08 September 2020