Morphological and etiological analyses of C3 and non-C3 glomerulonephritis in primary membranoproliferative glomerulonephritis using periodic acid-methenamine silver stain electron microscopy: a retrospective multicentered study

• Published in: Medical molecular morphology Vol. 57; no. 1; pp. 23 - 34
• Main Authors: Honma, Shiko, Sato, Naomi, Sakaguchi, Ryoko, Hashiguchi, Akinori, Uesugi, Noriko, Nakamura, Yasuhiro, Sasano, Hironobu, Joh, Kensuke
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01-03-2024; Springer Nature B.V
• Subjects: Anatomy; Glomerulonephritis; Immunoglobulins; Medicine; Medicine & Public Health; Microscopy; Molecular Medicine; Original Paper; Pathology; Transmission electron microscopy; Membranoproliferative glomerulonephritis type I; Renal biopsy; Membranoproliferative glomerulonephritis type III Burkholder subtype; C3 glomerulopathy; Membranoproliferative glomerulonephritis type III Anders and Strife subtype; Periodic acid-methenamine silver; Electron microscopy; C3 glomerulonephritis
• ISSN: 1860-1480; 1860-1499
• DOI: 10.1007/s00795-023-00370-z

This study elucidated the etiology of C3 glomerulonephritis (C3GN) and non-C3GN with primary membranoproliferative glomerulonephritis (MPGN) using transmission electron microscopy (TEM) and periodic acid-methenamine silver stain (PAM-EM). Thirty-one primary MPGN cases were analyzed by TEM and PAM-EM to distinguish among MPGN I, MPGN II, MPGN III Burkholder subtype (MPGN IIIB), and Anders and Strife subtype (MPGN IIIA/S). Each case was also classified into C3GN or non-C3GN according to the standard C3GN definition using immunostaining. Four cases of MPGN II met C3 glomerulopathy; whereas, four cases of MPGN IIIB did not meet C3 glomerulopathy. Seven of 11 cases (64%) of MPGN I without GBM disruption and 7 of 12 cases (58%) of MPGN IIIA/S with GBM disruption met the non-C3GN criteria with significant immunoglobulins’ deposition. Regardless of the C3GN or non-C3GN diagnosis, the deposits in primary MPGN I and MPGN IIIA/S exhibited ill-defined, amorphous, and foggy characteristics similar to those found in postinfectious GN but were different from immune complex (IC) deposits seen in MPGN IIIB. Not only C3GN but also non-C3GN was due to mechanisms other than IC deposition as found in postinfectious GN. Consequently, GBM disruption of MPGN IIIA/S was not due to IC deposition.