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Complement activation is associated with crescent formation in IgA nephropathy

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Abstract

IgA nephropathy (IgAN) is common chronic glomerulonephritis with variable prognosis, ranging from minor urinary abnormalities to end-stage renal disease. The revised Oxford classification of IgAN explains that cellular/fibrocellular crescents are associated with poor renal prognosis, proposing an extension to the MEST-C score. C3 immunofluorescent staining follows a distribution similar to IgA staining. Therefore, complement activation was reported to play a pivotal role in IgAN pathogenesis. This study included 132 IgAN patients diagnosed by renal biopsies. The clinical parameters at the time of the biopsies were obtained from patient data records. We classified the patients into C ≥ 1 and C0 groups, and compared clinical, light microscopic, and immunofluorescent features. In the C ≥ 1 group, 2 (1.5%) and 31 (23.5%) patients were assigned to C2 and C1, respectively. The remaining 99 patients (75%) were classified as C0. The C ≥ 1 group had lower average age and rate of hypertension, and higher score of urinary occult blood and E score. The C ≥ 1 group had significantly higher average immunofluorescence scores for IgA, C5b-9, mannose-associated serine protease (MASP) 1/3, MASP2, properdin, factor B, and kappa. The steroid use rate was significantly higher in the C ≥ 1 group. During the follow-up period of 2.90 years on average, the rate of renal dysfunction was not significantly different between groups. Crescent formation in IgAN was associated with activation of the lectin and alternative pathways. The C ≥ 1 group had significantly increased use of steroids, which probably caused comparable renal function during the follow-up period.

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Acknowledgments

The authors thank Ms. Yoko Sekita-Hatakeyama and Ms. Aya Sugimoto (Department of Diagnostic Pathology, Nara Medical University) for their technical assistance.

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Authors and Affiliations

  1. Department of Diagnostic Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, Japan

    Hiroe Itami, Kinta Hatakeyama & Chiho Ohbayashi

  2. Department of Diagnostic Pathology, Kobe City Medical Center General Hospital, Kobe, Japan

    Shigeo Hara

  3. Department of Nephrology, Nara Medical University, Kashihara, Japan

    Kenichi Samejima, Hideo Tsushima & Kazuhiko Tsuruya

  4. Department of Nephrology, Nara Prefecture General Medical Center, Nara, Japan

    Katsuhiko Morimoto

  5. Department of Nephrology, Saiseikai Suita Hospital, Suita, Japan

    Keisuke Okamoto

  6. Department of Nephrology, Nara Prefectural Seiwa Medical Center, Sango, Japan

    Takaaki Kosugi

  7. Department of Diabetes, Minami-Nara General Medical Center, Oyodo, Japan

    Takahiro Kawano & Kengo Fujiki

  8. Department of Internal Medicine, Saiseikai Chuwa Hospital, Sakurai, Japan

    Hiromichi Kitada

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  1. Hiroe Itami
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Contributions

HI and SH conceived and planned the study. KS, HT, KM, KO, TK, TK, KF, HK, and KT provided the clinical data and renal tissue samples. HI, KS, and HT carried out the immunofluorescence and scoring. HI carried out the statistical analysis. HI and SH contributed to the interpretation of the results. HI wrote the manuscript with the support of SH. CO, KT, and KH gave the final approval of the manuscript. All the authors critically reviewed and approved the manuscript.

Corresponding author

Correspondence to Hiroe Itami.

Ethics declarations

The study protocol was approved by the Ethics Committee of Nara Medical University and conducted in accordance with the tenets of the Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Supplementary Fig. 1

Representative immunofluorescence staining pattern of immunoglobulins (IgG, IgM, lambda), IgA subclass (IgA1, IgA2), fibrinogen, complements (C1q, C3, C4, C4d) and components related to complement activation (MBL, properdin, factor B). (PNG 4041 kb).

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Itami, H., Hara, S., Samejima, K. et al. Complement activation is associated with crescent formation in IgA nephropathy. Virchows Arch 477, 565–572 (2020). https://doi.org/10.1007/s00428-020-02800-0

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  • DOI: https://doi.org/10.1007/s00428-020-02800-0

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