Revisiting proliferative glomerulonephritis with monoclonal immunoglobulin deposits through immunoglobulin repertoire sequencing

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[1] Javaugue V, Pascal V, Nasr SH, et al. Revisiting proliferative glomerulonephritis with monoclonal immunoglobulin deposits through immunoglobulin repertoire sequencing. Kidney Int. 2025;108(6):1146-1157. doi:10.1016/j.kint.2025.07.039

Blogged by Nicolas Kozakowski, January 2nd, 2026

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID), originally described as a proliferative GN with monotypic IgG deposits, most often IgG3, is now classified as a monoclonal gammopathy of renal significance–associated disease. Given its rarity, renal pathologists consider PGNMID a diagnostic trophy. Yet, the true prey often remains elusive, as a circulating monoclonal immunoglobulin or the causative clone is rarely captured.

Using a highly sensitive high-throughput sequencing assay for immunoglobulin mRNA, investigators recently embarked on a systematic clone hunt in a multicentre PGNMID cohort, supplemented by proteomics and immunofluorescence. Their expedition uncovered an attributable clonal proliferation matching the biopsy findings in roughly one quarter of cases, while the majority yielded no such quarry. Further tracking using antibodies against light-chain variable domains revealed that clone-positive cases showed variable-domain restriction, whereas clone-negative cases displayed a heterogeneous pattern, suggesting oligoclonal deposits.

These findings imply that many cases currently labelled PGNMID may represent antigen-driven oligoclonal immune responses rather than true monoclonal gammopathies and may warrant reclassification.