Proliferative glomerulonephritis with monoclonal IgG3 deposits: A case series

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) caused by IgG3-dominant is rare and incompletely characterized. We retrospectively reported seven male patients (median age 63 years) with IgG3-dominant monoclonal immunoglobulin-associated glomerulonephritis. All patients presented with proteinuria (1.2-16.4 g/24 h), five with nephrotic-range proteinuria, and serum creatinine at diagnosis ranged from 88 to 294 μmol/L. Serum immunofixation electrophoresis was negative in all cases, while urinary free light chains were variably increased. Renal biopsy predominantly demonstrated a membranoproliferative glomerulonephritis pattern (6/7), frequently accompanied by crescents and variable degrees of chronic glomerulosclerosis. Immunofluorescence consistently showed dominant IgG3 deposition. Therapeutic approaches included supportive therapy, corticosteroids combined with cyclophosphamide, ripertamab-based regimens, and bortezomib. Renal outcomes were heterogeneous, ranging from sustained remission to progression to end-stage renal disease or death from severe infectious complications. Patients receiving bortezomib-based clone-directed therapy achieved the most reduction in proteinuria. These findings highlight the marked clinicopathological heterogeneity of IgG3-dominant PGNMID and underscore the importance of early recognition, assessment of chronic histologic injury, and individualized clone-directed treatment to improve renal outcomes.