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CD16+CD56+ cells are a potential culprit for hematuria in IgA nephropathy

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Abstract

Background

Hematuria is the first manifestation of urinary abnormality in immunoglobulin A nephropathy (IgAN). Hematuria has recently been reported as a risk factor for deterioration of renal function; however, its cause remains unknown.

Methods

We analyzed the surface marker of peripheral blood mononuclear cells before and immediately after tonsillectomy in IgAN patients and controls (chronic tonsillitis or tonsillar hypertrophy) by flow cytometry and investigated the association with hematuria. To prove our hypothesis that NK cells induce hematuria, we administered IL-12, activator of NK cells, to HIGA mice. In addition, we transferred cultured NK cells to nude rats and transferred the CD16+CD56+ cells, including NK cells, that are derived from the peripheral blood of IgAN patients immediately after tonsillectomy to nude rats to assess the hematuria level and renal histology of the recipients. We also performed cytotoxicity assays against glomerular endothelial cells by NK cells.

Results

We found that IgAN patients who showed rapid deterioration of hematuria after tonsillectomy also displayed a significant increase in CD16+CD56+ cells in the peripheral blood immediately after tonsillectomy. Exogenous administration of IL-12 to HIGA mice induced hematuria. Adoptive transfer of either cells of an NK cell line, or of CD16+CD56+ cells derived from IgAN patients, into nude rats induced hematuria in the recipients. In vitro analysis showed that NK cells exert cytotoxic activity toward human glomerular endothelial cells in a dose-dependent manner.

Conclusions

CD16+CD56+ cells seem to be responsible for hematuria in IgAN.

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Acknowledgments

This study was supported by a Grant-in-Aid for Young Scientists B (18790562).

Conflict of interest

All authors have declared no competing interest.

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Authors and Affiliations

  1. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Hirotsugu Iwatani, Ryohei Yamamoto, Kenichiro Iio, Masayuki Mizui, Hiromi Rakugi & Yoshitaka Isaka

  2. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan

    Yasuyuki Nagasawa

  3. Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Japan

    Arata Horii, Tadashi Kitahara & Hidenori Inohara

  4. Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Japan

    Atsushi Kumanogoh

  5. Nakayamadera Imai Clinic, Takarazuka, Japan

    Enyu Imai

Authors
  1. Hirotsugu Iwatani
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  2. Yasuyuki Nagasawa
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  3. Ryohei Yamamoto
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  4. Kenichiro Iio
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  5. Masayuki Mizui
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  6. Arata Horii
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  7. Tadashi Kitahara
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  8. Hidenori Inohara
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  9. Atsushi Kumanogoh
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  10. Enyu Imai
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  11. Hiromi Rakugi
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  12. Yoshitaka Isaka
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Corresponding author

Correspondence to Yoshitaka Isaka.

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Iwatani, H., Nagasawa, Y., Yamamoto, R. et al. CD16+CD56+ cells are a potential culprit for hematuria in IgA nephropathy. Clin Exp Nephrol 19, 216–224 (2015). https://doi.org/10.1007/s10157-014-0968-z

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  • DOI: https://doi.org/10.1007/s10157-014-0968-z

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