IgG4-to-IgG Ratio and Orbital Involvement Predict Clinical Response to B Cell Depletion in IgG4-Related Disease

IgG4-related disease (RD) demonstrates ethnic variations in phenotype, but data from diverse US populations are limited. We characterized ethnic differences in organ involvement and evaluated predictors of treatment response in a multiethnic cohort.

We conducted a retrospective study of 58 patients meeting 2019 American College of Rheumatology/EULAR criteria at Northwell Health (2011-2023). Data on demographics, organ involvement, histopathology, treatment, and serology (IgG4-to-IgG ratios) were analyzed. Response was assessed using Carruthers' Index.

The cohort included 43.1% White, 24.1% Asian, 19.0% Hispanic, and 13.8% Black patients. Organ involvement patterns were consistent across races, with lymph nodes (22.4%), orbital/lacrimal (20.7%), and retroperitoneum (20.7%) being most affected. Higher disease burden was observed in Asian patients (1.93 vs 1.44-1.64 organs, P = 0.058). A striking disparity in rituximab use was observed (0% in Black patients vs 57%-76% in others, P = 0.002), whereas disease phenotype distribution was otherwise similar across groups. Favorable response rates were high and comparable across all racial and ethnic groups (78.6%-100%, P = 0.462). In patients treated with rituximab (n = 35), a reduction in IgG4-to-IgG ratio predicted response (area under the curve = 0.806), outperforming baseline ratios. Orbital/lacrimal involvement was strongly associated with treatment failure (75% of nonresponders vs 13.3% of responders; odds ratio 6.6, 95% confidence interval 1.4-31.9, P = 0.03).

In a diverse IgG4-RD cohort, disease phenotypes were consistent across races, though treatment access disparities existed. Dynamic changes in IgG4-to-IgG ratios and the presence of orbital disease are key predictors of response to rituximab, informing personalized treatment strategies.