In-Depth Serum Proteomics by DIA-MS with In Silico Spectral Libraries Reveals Dynamics during the Active Phase of Systemic Juvenile Idiopathic Arthritis

Hironori Sato; Yuzaburo Inoue; Yusuke Kawashima; Daisuke Nakajima; Masaki Ishikawa; Ryo Konno; Ren Nakamura; Daigo Kato; Kanako Mitsunaga; Takeshi Yamamoto; Akiko Yamaide; Minako Tomiita; Akira Hoshioka; Osamu Ohara; Naoki Shimojo

doi:10.1021/acsomega.1c06681

In-Depth Serum Proteomics by DIA-MS with In Silico Spectral Libraries Reveals Dynamics during the Active Phase of Systemic Juvenile Idiopathic Arthritis

ACS Omega. 2022 Feb 15;7(8):7012-7023. doi: 10.1021/acsomega.1c06681. eCollection 2022 Mar 1.

Authors

Hironori Sato^{1

2}, Yuzaburo Inoue^{3

4}, Yusuke Kawashima¹, Daisuke Nakajima¹, Masaki Ishikawa¹, Ryo Konno¹, Ren Nakamura¹, Daigo Kato³, Kanako Mitsunaga³, Takeshi Yamamoto^{3

5}, Akiko Yamaide³, Minako Tomiita⁶, Akira Hoshioka³, Osamu Ohara¹, Naoki Shimojo⁷

Affiliations

¹ Department of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan.
² Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Chiba 260-8677, Japan.
³ Department of Allergy and Rheumatology, Chiba Children's Hospital, Chiba, Chiba 266-0007, Japan.
⁴ Division of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba, Chiba 260-8717, Japan.
⁵ Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101-2795, United States.
⁶ Department of Clinical Research, National Hospital Organization Shimoshizu National Hospital, Yotsukaido, Chiba 284-0003, Japan.
⁷ Center for Preventive Medical Sciences, Chiba University, Chiba, Chiba 263-8522, Japan.

Abstract

In serum proteomics using mass spectrometry, the number of detectable proteins is reduced due to high-abundance proteins, such as albumin. However, recently developed data-independent acquisition mass spectrometry (DIA-MS) proteomics technology has made it possible to remarkably improve the number of proteins in a serum analysis by removing high-abundance proteins. Using this technology, we analyzed sera from patients with systemic juvenile idiopathic arthritis (sJIA), a rare pediatric disease. As a result, we identified 2727 proteins with a wide dynamic range derived from various tissue leakages. We also selected 591 proteins that differed significantly in their active phases. These proteins were involved in many inflammatory processes, and we also identified immunoproteasomes, which were not previously found in serum, suggesting that they may be involved in the pathogenesis of sJIA. A detailed high-depth DIA-MS proteomic analysis of serum may be useful for understanding the pathogenesis of sJIA and may provide clues for the development of new biomarkers.