A serum #IgG4 cut off level of 135 mg/dl has been incorporated into the original Comprehensive Diagnostic criteria as well as the 2020 Revised Comprehensive Diagnostic criteria for IgG4-related disease (IgG4-RD). However, although elevated serum IgG4 levels are commonly observed in IgG4-RD and serve as a useful supportive marker, but they are not a gold standard for diagnosis due to variable performance (sensitivity 51-80%, specificity 60%). In addition to traditional #biomarkers like serum IgG4 levels and characteristic histology, several novel indicators —including IgG2, serum soluble IL-2 receptor (sIL-2R), and CCL18— can help diagnose IgG4-RD more accurately and predict treatment response by reflecting inflammation and fibrosis. Ongoing research is focused on identifying specific autoantigens and exploring new potential biomarkers, such as various serological and histopathological immune cells (macrophages, mast cells, T and B cell subsets, and pathways like I-IFN/IL-33). Due to the frequent multi-organ involvement in IgG4-RD, non-invasive PET-CT imaging is also valuable for improving diagnosis and differential diagnosis. *Adapted from: Umehara H, Okazaki K, Kawa S, et al. The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. Mod Rheumatol. 2021;31(3):529-533. 🔗doi.org/10.1080/14397595.202…