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Membranoproliferative pattern of glomerular injury associated with complement component 9 deficiency due to Arg95Stop mutation

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Abstract

Background

Arg95Stop mutation of exon 4 in complement component 9 (C9) gene is common in individuals in Japan with C9 deficiency (C9D); however, understanding of the influences of C9D on human glomerulonephritis remains elusive.

Methods

A total of 1288 patients with chronic kidney disease (CKD) were recruited from the hospitals in Niigata prefecture. They were screened for the Arg95Stop mutation of C9 gene by allele-specific PCR.

Results

We identified two individuals with C9D among 1,288 CKD patients, a frequency comparable to that of the general Japanese population (0.16%). Case 1 involved a 44-year-old man presenting with nephrotic proteinuria. The hemolytic activity of CH50 was low, and the concentration of C9 was not detected. Sequencing of exon 4 of the C9 gene showed the Arg95Stop mutation. Renal biopsy revealed diffuse global mesangial proliferation with extensive duplication of glomerular capillary walls. Mesangial, subendothelial and subepithelial deposits were noticed with light and electron microscopy. Immunofluorescent study showed predominant mesangial IgA deposition. Case 2 involved a 62-year-old man presenting with proteinuria and hematuria. His CH50 level was decreased. Renal biopsy revealed diffuse global mesangial proliferation with extensive duplication of glomerular capillary walls. Immune deposits were also confirmed. The percentage of C9D among patients with mesangial proliferation and duplication of GBM in this study was 5.1%.

Conclusion

These results suggested that the lack of membrane attack complex because of an Arg95Stop mutation of the C9 gene predisposed patients to pathognomonic glomerulonephritis.

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research on Priority Areas (no. 20018009 to I. Narita), a Grant-in-Aid for Scientific Research B (no. 20390234 to I. Narita) and a Grant-in-Aid for Scientific Research C (no. 20590951 to S. Goto) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We gratefully acknowledge the excellent technical assistance of Naofumi Imai, Yao Feifei and Katsura Minowa.

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Authors and Affiliations

  1. Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, 951-8510, Japan

    Takayoshi Miura, Shin Goto, Seitaro Iguchi, Hisaki Shimada, Mitsuhiro Ueno & Ichiei Narita

  2. Department of Clinical Nephroscience, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Shin Goto

  3. Blood Purification Center, Niigata University Hospital, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan

    Shin-ichi Nishi

Authors
  1. Takayoshi Miura
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  2. Shin Goto
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  3. Seitaro Iguchi
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  4. Hisaki Shimada
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  5. Mitsuhiro Ueno
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  6. Shin-ichi Nishi
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  7. Ichiei Narita
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Correspondence to Shin Goto.

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Miura, T., Goto, S., Iguchi, S. et al. Membranoproliferative pattern of glomerular injury associated with complement component 9 deficiency due to Arg95Stop mutation. Clin Exp Nephrol 15, 86–91 (2011). https://doi.org/10.1007/s10157-010-0358-0

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  • DOI: https://doi.org/10.1007/s10157-010-0358-0

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