Stratifin as a novel diagnostic biomarker in serum for diffuse alveolar damage

Noriaki Arakawa, Atsuhito Ushiki, Mitsuhiro Abe, Shinichiro Matsuyama, Yoshinobu Saito, Takeru Kashiwada, Yasushi Horimasu, Akihiko Gemma, Koichiro Tatsumi, Noboru Hattori, Kenji Tsushima, Keiko Miyashita, Kosuke Saito, Ryosuke Nakamura, Takeshi Toyoda, Kumiko Ogawa, Motonobu Sato, Kazuhiko Takamatsu, Kazuhiko Mori, Takayoshi Nishiya, Takashi Izumi, Yasuo Ohno, Yoshiro Saito () and Masayuki Hanaoka
Additional contact information
Noriaki Arakawa: National Institute of Health Sciences
Atsuhito Ushiki: Shinshu University School of Medicine
Mitsuhiro Abe: Chiba University
Shinichiro Matsuyama: National Institute of Health Sciences
Yoshinobu Saito: Nippon Medical School
Takeru Kashiwada: Nippon Medical School
Yasushi Horimasu: Hiroshima University Hospital
Akihiko Gemma: Nippon Medical School
Koichiro Tatsumi: Chiba University
Noboru Hattori: Hiroshima University
Kenji Tsushima: International University of Health and Welfare
Keiko Miyashita: National Institute of Health Sciences
Kosuke Saito: National Institute of Health Sciences
Ryosuke Nakamura: National Institute of Health Sciences
Takeshi Toyoda: National Institute of Health Sciences
Kumiko Ogawa: National Institute of Health Sciences
Motonobu Sato: Astellas Pharma Inc
Kazuhiko Takamatsu: Astellas Pharma Inc
Kazuhiko Mori: Daiichi Sankyo RD Novare Co., Ltd
Takayoshi Nishiya: Daiichi Sankyo RD Novare Co., Ltd
Takashi Izumi: Kihara Memorial Foundation
Yasuo Ohno: Kihara Memorial Foundation
Yoshiro Saito: National Institute of Health Sciences
Masayuki Hanaoka: Shinshu University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Among the various histopathological patterns of drug-induced interstitial lung disease (DILD), diffuse alveolar damage (DAD) is associated with poor prognosis. However, there is no reliable biomarker for its accurate diagnosis. Here, we show stratifin/14-3-3σ (SFN) as a biomarker candidate found in a proteomic analysis. The study includes two independent cohorts (including totally 26 patients with DAD) and controls (total 432 samples). SFN is specifically elevated in DILD patients with DAD, and is superior to the known biomarkers, KL-6 and SP-D, in discrimination of DILD patients with DAD from patients with other DILD patterns or other lung diseases. SFN is also increased in serum from patients with idiopathic DAD, and in lung tissues and bronchoalveolar lavage fluid of patients with DAD. In vitro analysis using cultured lung epithelial cells suggests that extracellular release of SFN occurs via p53-dependent apoptosis. We conclude that serum SFN is a promising biomarker for DAD diagnosis.

Date: 2022
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DOI: 10.1038/s41467-022-33160-9

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