Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits: A Polyclonal Beginning with a Monoclonal Plot Twist

Introduction: Proliferative Glomerulitis with Monoclonal Immunoglobulin Deposits (PGNMID) is characterized by M protein deposits in glomeruli that cause inflammation and injury by complement activation. The upstream mechanisms of M protein production remain unclear. Less than 30% of cases have detectable M protein or bone marrow clone. Furthermore, it is extremely rare that patients present with an initial polyclonal immune complex mediated glomerulonephritis (PICGN) that subsequently evolves into PGNMID. We herein present 2 cases of membranous PICGN who later developed PGNMID despite immunosuppressive treatment. Case Description: Patient-1: A 30-year-old man without past medical history presented with acute kidney injury and fluid overload. He had positive antinuclear antibodies with nephrotic syndrome and was found to have a membranous PICGN on biopsy diagnosed as class V lupus nephritis (LN). He was treated with mycophenolate mofetil and steroids with partial remission but developed worsening renal function and recurrent nephrotic syndrome 3 years later. This led to a subsequent kidney biopsy with membranous and crescentic IgG1k PGNMID. He was treated with cyclophosphamide without remission and enrolled in a clinical trial with daratumumab. Patient-2: A 56-year-old woman with a history of systemic lupus and class V LN suffered a flare of recurrent cerebritis and nephritis. A proliferative and membranous PICGN attributed to lupus was seen on biopsy. She was treated with cyclophosphamide and remained in remission with maintenance immunosuppression, but 5 years later developed worsening proteinuria and renal function. Repeat kidney biopsy showed membranous IgG1k PGNMID. Belimumab was added to her immunosuppressive regimen, and she remains in partial remission. Discussion: PGNMID is a monoclonal-related histopathological entity that is not only associated with hematolymphoid neoplasms but also with infections, solid tumors, autoimmune diseases and other disorders of persistent antigen exposure. However, transformation of PICGN to PGNMID is rarely described. Two previously described cases had an interval biopsy with polyclonal staining dominant for the eventual culprit monoclonal Ig, suggesting a poly to monoclonal GN evolution. Although the pathogenesis of PGNMID remains unclear, our cases provide more evidence that it can arise from an initial PICGN such as lupus nephritis.