Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis

Abstract Background Anti-melanoma differentiation-associated gene five antibody positive (MDA5+) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate...

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Main Authors: Yulu Qiu, Xiaoke Feng, Chang Liu, Yumeng Shi, Lingxiao Xu, Hanxiao You, Lei Wang, Chengyin Lv, Fang Wang, Wenfeng Tan
Format: Article
Language:English
Published: BMC 2024-01-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13075-023-03243-z
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author Yulu Qiu
Xiaoke Feng
Chang Liu
Yumeng Shi
Lingxiao Xu
Hanxiao You
Lei Wang
Chengyin Lv
Fang Wang
Wenfeng Tan
author_facet Yulu Qiu
Xiaoke Feng
Chang Liu
Yumeng Shi
Lingxiao Xu
Hanxiao You
Lei Wang
Chengyin Lv
Fang Wang
Wenfeng Tan
author_sort Yulu Qiu
collection DOAJ
description Abstract Background Anti-melanoma differentiation-associated gene five antibody positive (MDA5+) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate prognostic factors for RP-ILD in MDA5+ DM patients. Methods Plasma samples from 20 MDA5+ DM patients and 10 healthy controls (HC) were collected for proteomic analysis using liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis. The proteins of interest were validated in independent samples (20 HC, 20 MDA5+ DM with RP-ILD, and 20 non-RP-ILD patients) with enzyme-linked immunosorbent assay (ELISA). Results A total of 413 differentially expressed proteins (DEPs) were detected between the MDA5+ DM patients and HC. When comparing DEPs between RP-ILD and non-RP-ILD patients, 79 proteins were changed in RP-ILD patients, implicating acute inflammatory response, coagulation, and complement cascades. Six candidate biomarkers were confirmed with ELISA. Secreted phosphoprotein 1 (SPP1), serum amyloid A1 (SAA1), and Kininogen 1 (KNG1) concentrations were significantly elevated in RP-ILD patients than those in non-RP-ILD patients and HC. In the different clinical subgroups, SPP1 was particularly elevated in the high-risk RP-ILD subgroup of MDA5+ DM. Conclusion This study provides novel insights into the pathogenesis of RP-ILD development in MDA5+ DM and suggests the plasma protein SPP1 could serve as a potential blood biomarker for RP-ILD early warning.
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spelling doaj.art-c218df4eff024779b6e7fc7a92aec3442024-01-07T12:38:01ZengBMCArthritis Research & Therapy1478-63622024-01-0126111210.1186/s13075-023-03243-zProteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositisYulu Qiu0Xiaoke Feng1Chang Liu2Yumeng Shi3Lingxiao Xu4Hanxiao You5Lei Wang6Chengyin Lv7Fang Wang8Wenfeng Tan9Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background Anti-melanoma differentiation-associated gene five antibody positive (MDA5+) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate prognostic factors for RP-ILD in MDA5+ DM patients. Methods Plasma samples from 20 MDA5+ DM patients and 10 healthy controls (HC) were collected for proteomic analysis using liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis. The proteins of interest were validated in independent samples (20 HC, 20 MDA5+ DM with RP-ILD, and 20 non-RP-ILD patients) with enzyme-linked immunosorbent assay (ELISA). Results A total of 413 differentially expressed proteins (DEPs) were detected between the MDA5+ DM patients and HC. When comparing DEPs between RP-ILD and non-RP-ILD patients, 79 proteins were changed in RP-ILD patients, implicating acute inflammatory response, coagulation, and complement cascades. Six candidate biomarkers were confirmed with ELISA. Secreted phosphoprotein 1 (SPP1), serum amyloid A1 (SAA1), and Kininogen 1 (KNG1) concentrations were significantly elevated in RP-ILD patients than those in non-RP-ILD patients and HC. In the different clinical subgroups, SPP1 was particularly elevated in the high-risk RP-ILD subgroup of MDA5+ DM. Conclusion This study provides novel insights into the pathogenesis of RP-ILD development in MDA5+ DM and suggests the plasma protein SPP1 could serve as a potential blood biomarker for RP-ILD early warning.https://doi.org/10.1186/s13075-023-03243-zDermatomyositisMDA5Interstitial lung diseaseRP-ILDBiomarker
spellingShingle Yulu Qiu
Xiaoke Feng
Chang Liu
Yumeng Shi
Lingxiao Xu
Hanxiao You
Lei Wang
Chengyin Lv
Fang Wang
Wenfeng Tan
Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis
Arthritis Research & Therapy
Dermatomyositis
MDA5
Interstitial lung disease
RP-ILD
Biomarker
title Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis
title_full Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis
title_fullStr Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis
title_full_unstemmed Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis
title_short Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis
title_sort proteomic profiling identifies spp1 associated with rapidly progressive interstitial lung disease in anti mda5 positive dermatomyositis
topic Dermatomyositis
MDA5
Interstitial lung disease
RP-ILD
Biomarker
url https://doi.org/10.1186/s13075-023-03243-z
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