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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

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Abstract

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.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank Enago (www.enago.jp) for the English Language review.

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Authors and Affiliations

  1. Department of Pathology, School of Medicine, The Jikei University, Tokyo, Japan

    Shiko Honma, Ryoko Sakaguchi & Kensuke Joh

  2. Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai, Japan

    Naomi Sato & Hironobu Sasano

  3. Department of Pathology, Iwate Prefectural Central Hospital, Iwate, Japan

    Naomi Sato

  4. Department of Pathology, School of Medicine, Keio University, Tokyo, Japan

    Akinori Hashiguchi

  5. Department of Pathology, Fukuoka University of Medicine, Fukuoka, Japan

    Noriko Uesugi

  6. Faculty of Medicine, Division of Pathology, Tohoku Medical and Pharmaceutical University, Sendai, Japan

    Yasuhiro Nakamura

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  1. Shiko Honma
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  8. Kensuke Joh
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Contributions

HS, NS, YN, and KJ designed the study and analyzed the data. AH prepared micrographs of transmission electron microscopy (TEM) and PAM-EM. KJ shot electron micrographs of TEM and PAM-EM. SH and KJ measured the extent of glomerular basement membrane disruption. RS conducted statistical analysis. NS, RS, and NU corrected and cleaned up the clinical data. All authors approved the final version of the manuscript.

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Correspondence to Kensuke Joh.

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Honma, S., Sato, N., Sakaguchi, R. et al. 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. Med Mol Morphol 57, 23–34 (2024). https://doi.org/10.1007/s00795-023-00370-z

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