Effects of glucocorticoids on B-cell subpopulations in patients with IgG4-related disease

Objectives. Glucocorticoids induce prompt clinical improvement in patients with IgG4-related disease (IgG4-RD) but their mechanisms of action in this specific condition are not fully understood. B lymphocytes appear central to IgG4-RD pathogenesis because B-cell depletion with rituximab leads to swift clinical responses. In the present work we aim to assess the effects of glucocorticoids on B-cell subpopulations in patients with IgG4-RD. Methods. Fifty patients with active untreated IgG4-RD and 20 healthy controls were enrolled in the present study. Flow cytometry analysis for total circulating CD19(+) and CD20(+) cells, naive B cells, memory B cells, plasmablasts, and plasma cells was performed at baseline in all patients, and after 6 months of glucocorticoid treatment in 30 patients. Correlation studies with biomarkers of disease activity were also performed. Results. At baseline, patients with IgG4-RD showed reduced CD19(+) and CD20(+) B cells compared to healthy controls, but increased circulating plasmablasts and plasma cells. Circulating plasmablasts and plasma cells correlated with clinical and serological biomarkers of IgG4-RD activity. Glucocorticoid-induced disease remission was accompanied by a reduction of naive B cell count, an increase of memory B cells, and by a depletion of circulating plasmablasts and plasma cells. CD19(+) and CD20(+) B cells, were not affected by glucocorticoids. Conclusions. The efficacy of glucocorticoids in IgG4-RD is associated with selective effects on different B-cell subpopulations. Further studies are warranted to fully understand possible perturbations of the naive and memory B-cell compartments in patients with IgG4-RD.