Serum peptides as candidate biomarkers for relapsing polychondritis

Introduction: Relapsing polychondritis (RP) is an intractable disease characterized by recurrent inflammation of cartilaginous tissue throughout the body. It is difficult to accurately diagnose RP, and no useful biomarkers have yet been identified. Objectives: We analyzed serum peptide profiles to i...

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Main Authors: Toshiyuki Sato, Masaaki Sato, Kouhei Nagai, Masahiko Fukasawa, Yoshiaki Nagashima, Teisuke Uchida, Atsuhiro Tsutiya, Kazuki Omoteyama, Mitsumi Arito, Yukiko Takakuwa, Seido Ooka, Naoya Suematsu, Kimito Kawahata, Yoshihisa Yamano, Tomohiro Kato, Manae S. Kurokawa
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Journal of Mass Spectrometry and Advances in the Clinical Lab
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667145X25000082
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author Toshiyuki Sato
Masaaki Sato
Kouhei Nagai
Masahiko Fukasawa
Yoshiaki Nagashima
Teisuke Uchida
Atsuhiro Tsutiya
Kazuki Omoteyama
Mitsumi Arito
Yukiko Takakuwa
Seido Ooka
Naoya Suematsu
Kimito Kawahata
Yoshihisa Yamano
Tomohiro Kato
Manae S. Kurokawa
author_facet Toshiyuki Sato
Masaaki Sato
Kouhei Nagai
Masahiko Fukasawa
Yoshiaki Nagashima
Teisuke Uchida
Atsuhiro Tsutiya
Kazuki Omoteyama
Mitsumi Arito
Yukiko Takakuwa
Seido Ooka
Naoya Suematsu
Kimito Kawahata
Yoshihisa Yamano
Tomohiro Kato
Manae S. Kurokawa
author_sort Toshiyuki Sato
collection DOAJ
description Introduction: Relapsing polychondritis (RP) is an intractable disease characterized by recurrent inflammation of cartilaginous tissue throughout the body. It is difficult to accurately diagnose RP, and no useful biomarkers have yet been identified. Objectives: We analyzed serum peptide profiles to identify novel candidate biomarkers for RP. Methods: Thirty-seven patients with RP, 42 patients with rheumatoid arthritis (RA), and 35 healthy control (HC) subjects were divided into training and testing sets. Seven patients demonstrating granulomatosis with polyangiitis (GPA) were used for validation. The ion intensity of serum peptides was comprehensively measured by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry and applied to a supervised multivariate analysis. Peptides of interest were analyzed by liquid chromatography-tandem mass spectrometry. Results: In the training set, models developed based on 11 (RP/HC-11P model), 9 (RP/RA-9P model), and 14 (RP/nonRP-14P model) peptides, out of 160 peptides detected were able to completely discriminate the RP group from the HC, RA, and nonRP (HC + RA) groups. Almost all of the 15 identified discriminatory peptides comprising these models were fragments of proteins associated with coagulation. Four models, each consisting of 4 out of 10 identified peptides of the RP/nonRP-14P model (models RP/nonRP-4P-2, -10, -11, and -38), provided ≥ 70.0 % sensitivity and specificity when applied to the validation set (the testing set and the GPA group) (AUROC, 0.779–0.815). Notably, the RP/nonRP-4P-2 model provided 83.3 % sensitivity and 71.7 % specificity in the validation set (AUROC, 0.802). Conclusions: Serum peptides are useful as candidate biomarkers for discriminating RP and may be involved in the pathophysiology of RP.
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spelling doaj-art-27dda54de61c47dba17fd5248856af5d2025-08-24T05:14:56ZengElsevierJournal of Mass Spectrometry and Advances in the Clinical Lab2667-145X2025-08-0137283810.1016/j.jmsacl.2025.04.001Serum peptides as candidate biomarkers for relapsing polychondritisToshiyuki Sato0Masaaki Sato1Kouhei Nagai2Masahiko Fukasawa3Yoshiaki Nagashima4Teisuke Uchida5Atsuhiro Tsutiya6Kazuki Omoteyama7Mitsumi Arito8Yukiko Takakuwa9Seido Ooka10Naoya Suematsu11Kimito Kawahata12Yoshihisa Yamano13Tomohiro Kato14Manae S. Kurokawa15Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, JapanClinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, JapanDepartment of Genetic Engineering, Faculty of Biology-Oriented Science and Technology, Kindai University, Kinokawa, Wakayama, JapanDepartment of Otolaryngology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, JapanDisease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, JapanDisease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, JapanClinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, JapanClinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, JapanClinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, JapanDepartment of Rheumatology and Allergology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, JapanDepartment of Rheumatology and Allergology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, JapanClinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, JapanDepartment of Rheumatology and Allergology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, JapanDepartment of Neurology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan; Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa, JapanClinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, JapanDisease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan; Corresponding author at: Disease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.Introduction: Relapsing polychondritis (RP) is an intractable disease characterized by recurrent inflammation of cartilaginous tissue throughout the body. It is difficult to accurately diagnose RP, and no useful biomarkers have yet been identified. Objectives: We analyzed serum peptide profiles to identify novel candidate biomarkers for RP. Methods: Thirty-seven patients with RP, 42 patients with rheumatoid arthritis (RA), and 35 healthy control (HC) subjects were divided into training and testing sets. Seven patients demonstrating granulomatosis with polyangiitis (GPA) were used for validation. The ion intensity of serum peptides was comprehensively measured by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry and applied to a supervised multivariate analysis. Peptides of interest were analyzed by liquid chromatography-tandem mass spectrometry. Results: In the training set, models developed based on 11 (RP/HC-11P model), 9 (RP/RA-9P model), and 14 (RP/nonRP-14P model) peptides, out of 160 peptides detected were able to completely discriminate the RP group from the HC, RA, and nonRP (HC + RA) groups. Almost all of the 15 identified discriminatory peptides comprising these models were fragments of proteins associated with coagulation. Four models, each consisting of 4 out of 10 identified peptides of the RP/nonRP-14P model (models RP/nonRP-4P-2, -10, -11, and -38), provided ≥ 70.0 % sensitivity and specificity when applied to the validation set (the testing set and the GPA group) (AUROC, 0.779–0.815). Notably, the RP/nonRP-4P-2 model provided 83.3 % sensitivity and 71.7 % specificity in the validation set (AUROC, 0.802). Conclusions: Serum peptides are useful as candidate biomarkers for discriminating RP and may be involved in the pathophysiology of RP.http://www.sciencedirect.com/science/article/pii/S2667145X25000082Biological markersMass spectrometryRelapsing polychondritisSerum peptides
spellingShingle Toshiyuki Sato
Masaaki Sato
Kouhei Nagai
Masahiko Fukasawa
Yoshiaki Nagashima
Teisuke Uchida
Atsuhiro Tsutiya
Kazuki Omoteyama
Mitsumi Arito
Yukiko Takakuwa
Seido Ooka
Naoya Suematsu
Kimito Kawahata
Yoshihisa Yamano
Tomohiro Kato
Manae S. Kurokawa
Serum peptides as candidate biomarkers for relapsing polychondritis
Journal of Mass Spectrometry and Advances in the Clinical Lab
Biological markers
Mass spectrometry
Relapsing polychondritis
Serum peptides
title Serum peptides as candidate biomarkers for relapsing polychondritis
title_full Serum peptides as candidate biomarkers for relapsing polychondritis
title_fullStr Serum peptides as candidate biomarkers for relapsing polychondritis
title_full_unstemmed Serum peptides as candidate biomarkers for relapsing polychondritis
title_short Serum peptides as candidate biomarkers for relapsing polychondritis
title_sort serum peptides as candidate biomarkers for relapsing polychondritis
topic Biological markers
Mass spectrometry
Relapsing polychondritis
Serum peptides
url http://www.sciencedirect.com/science/article/pii/S2667145X25000082
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