Myeloperoxidase-Associated Membranous Nephropathy in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis

Abstract

IntroductionAnti-neutrophil cytoplasmic antibody (ANCA)–associated glomerulonephritis (GN) is characterized by pauci-immune crescentic GN. Although myeloperoxidase ANCA-associated GN (MPO-ANCA GN) with membranous nephropathy (MN), where bright granular capillary myeloperoxidase (MPO) and immunoglobulin G (IgG) staining along the glomerular basement membrane (GBM) is present, has been reported; however, its clinicopathological features remain unclear. MethodsWe investigated 7 MPO-ANCA GN with MN and 11 control cases (6 MPO-ANCA GN and 5 primary MN cases). Proteomics of laser microdissected glomeruli followed by immunohistochemical analysis was performed to identify causal antigens in MPO-ANCA GN with MN. We described the clinicopathological features of MPO-associated MN compared with those of MPO-ANCA GN and primary MN. ResultsWe detected proteomic MPO and granular capillary MPO deposits in all MPO-ANCA GN with MN cases. Confocal microscopy revealed MPO and IgG co-localization along the GBM. MPO-associated MN clinicopathological features include greater proteinuria, a higher fibrous crescent rate, and a lower MPO-ANCA titer than MPO-ANCA GN. The estimated glomerular filtration rate and urinary protein excretion were lower in MPO-associated MN than in primary MN. ConclusionMPO-associated MN, a unique type of secondary MN where MPO serves as the causal antigen, is a subset of MPO-ANCA GN with MN. Prolonged periods of MPO-ANCA GN and a low MPO-ANCA titer might be related to MPO-associated MN development.