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Urinary Activin A is a novel biomarker reflecting renal inflammation and tubular damage in ANCA-associated vasculitis


Autoři: Yoshinori Takei aff001;  Shunsuke Takahashi aff001;  Masao Nakasatomi aff001;  Toru Sakairi aff001;  Hidekazu Ikeuchi aff001;  Yoriaki Kaneko aff001;  Keiju Hiromura aff001;  Yoshihisa Nojima aff002;  Akito Maeshima aff001
Působiště autorů: Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, Maebashi, Japan aff001;  Department of Nephrology and Rheumatology, Japanese Red Cross Hospital, Maebashi, Japan aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223703

Souhrn

Activin A, a member of the transforming growth factor-beta superfamily, is a critical modulator of inflammation and plays a key role in controlling the cytokine cascade that drives the inflammatory response. However, the role of activin A in inflammatory kidney diseases remains unknown. To address this issue, we examined here whether activin A can be detected in the kidney and/or urine from patients with antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV). Fifty-one patients who had been diagnosed with AAV and were treated in our department between November 2011 to March 2018 were included in this study. Forty-one patients had renal complications (renal AAV). Serum and urinary activin A levels were measured by enzyme-linked immunosorbent assay. Correlation of urinary activin A concentration with clinical parameters was analyzed. Urinary activin A was undetectable in healthy volunteers. In contrast, urinary activin A concentration was significantly increased in patients with renal AAV but not in those with non-renal AAV. Urinary activin A concentration decreased rapidly after immunosuppressive treatment. There was a significant correlation of urinary activin A level with urinary protein, L-FABP, and NAG. Histologic evaluation revealed that urinary activin A levels were significantly higher in patients with cellular crescentic glomeruli than in those lacking this damage. In situ hybridization demonstrated that the mRNA encoding the activin A βA subunit was undetectable in normal kidneys but accumulated in the proximal tubules and crescentic glomeruli of the kidneys of patients with renal AAV. Immunostaining showed that activin A protein also was present in the proximal tubules, crescentic glomeruli, and macrophages infiltrating into the interstitium in the kidneys of patients with renal AAV. These data suggested that urinary activin A concentration reflects renal inflammation and tubular damage in AAV and may be a useful biomarker for monitoring renal AAV.

Klíčová slova:

Enzyme-linked immunoassays – Immunohistochemistry techniques – Immunostaining – In situ hybridization – Kidneys – Macrophages – Urine – Glomeruli


Zdroje

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