Proliferative glomerulonephritis with monoclonal immunoglobulin deposits: an entity associated with distinct diseases and comparison between IgG1 and IgG3 subtypes

OBJECTIVES: The aim of the study was to investigate the clinicopathological characteristics and prognosis of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and determine the differences between PGNMID associated with extrarenal disease and without clear etiology as well as the differences between IgG1 and IgG3 subtypes. METHODS: Data from 46 patients with PGNMID observed from January 2014 to September 2021 in Peking University First Hospital were retrospectively analyzed, including 36 patients without clear etiology (Group A) and 10 patients with extrarenal disease (Group B). RESULTS: At presentation patients showed proteinuria (95.7%), hematuria (89.1%), renal insufficiency (73.9%), and hypocomplementemia of C3 or C4 (35.6%). Monoclonal immunoglobulin or cell clones were detected in 22.2% of patients (10/45). The monoclonal immunoglobulins deposited in kidney were IgG3 in 40 patients, IgG1 in 5, and IgM in one. Monoclonal IgG1 deposits were more common in Group B than in Group A (4/10 vs. 1/36, p = 0.006). The intensity of glomerular C3 deposition and the frequency of subendothelial deposits in IgG3 subtype were significantly higher than those in IgG1 subtype. During a median follow-up time of 12.2 (range 1-61) months, a higher level of serum creatinine at biopsy and a higher percentage of global glomerulosclerosis were independent predictors of end-stage kidney disease. CONCLUSIONS: PGNMID associated with extrarenal disease was more likely to have monoclonal IgG1 deposits. PGNMID of IgG3 subtype differs from IgG1 subtype by higher intensity of glomerular C3 deposition and higher frequency of subendothelial deposits. Serum creatinine and global glomerulosclerosis were independent prognostic predictors of ESKD in PGNMID.