Diagnostic Utility of IgG Subtypes in monoclonal Membranous Glomerulopathy: Evidence of Heavy Chain Restriction

Document Type

Conference Proceeding

Publication Date

11-2025

Publication Title

American Journal of Clinical Pathology

Abstract

Introduction/Objective: Monoclonal membranous glomerulopathy (MGN) is a rare variant of monoclonal protein-associated nephropathy, reported in only a few cases, including a single case series of 26 patients. Notably, most of these cases lacked detectable monoclonal protein by serological tests or monoclonal plasma cells in bone marrow biopsies. However, they consistently demonstrated restricted expression of a single IgG heavy chain subtype (IgG2 or IgG3) via immunofluorescence, suggesting a potential diagnostic utility of the IgG1-4 panel in identifying monoclonal MGN. This study investigates the role of IgG1-4 sub - typing in diagnosing monoclonal MGN. Methods/Case Report: Three cases of monoclonal MGN confirmed through external consultation were included. These cases lacked serological or bone marrow evidence of monoclonal protein. IgG1-4 sub - typing was performed using immunofluorescence (IF). For comparison, three cases of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and ten cases of polyclonal glomerulopathies (including primary MGN and lupus nephritis) were included as controls. Results: The monoclonal MGN cases (two females and one male, aged in the range of 60–70 years) exhibited restricted staining for IgG2 or IgG3 . Similarly, all PGNMID cases demonstrated IgG3 restriction. In contrast, polyclonal primary MGN displayed strong IgG4 staining, consistent with positive glomerular PLA2R staining. Lupus nephritis showed staining for all IgG subtypes (IgG1-4), while secondary MGN cases varied, with one case showing IgG2 restriction and another exhibiting IgG1 and IgG2 positivity. The remaining polyclonal glomerulopathies were negative for all IgG1-4 stains. Conclusion: Conclusion: IgG heavy chain subtyping (IgG1-4) can demonstrate monoclonal IgG restriction in monoclonal MGN, sup - porting its diagnostic utility in cases lacking serological or bone marrow evidence of monoclonality. However, caution is warranted when interpreting restricted IgG staining in secondary MGN, as these cases may also exhibit restricted IgG subtypes. Polyclonality in secondary MGN can be distinguished by co-expression of kappa and lambda light chains. Further studies are warranted to validate these findings and refine diagnostic criteria for monoclonal MGN.

Volume

164

Issue

Suppl 1

First Page

S163

Comments

American Society for Clinical Pathology (ASCP) Annual Meeting, November 17-20, 2025, Atlanta, GA

Last Page

S164

DOI

10.1093/ajcp/aqaf121.392

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