Hierarchical cluster analysis of cytokine profiles reveals a cutaneous vasculitis-associated subgroup in dermatomyositis

Objectives Dermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference in cytokine profiles of different subsets in DM based on the disease activity and myositis-specific antibodies, and to identify the clinical...

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Published inClinical rheumatology Vol. 40; no. 3; pp. 999 - 1008
Main Authors Bai, Jingjing, Wu, Chanyuan, Zhong, Danli, Xu, Dong, Wang, Qian, Zeng, Xiaofeng
Format Journal Article
LanguageEnglish
Published Cham Springer International Publishing 01.03.2021
Springer Nature B.V
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Abstract Objectives Dermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference in cytokine profiles of different subsets in DM based on the disease activity and myositis-specific antibodies, and to identify the clinical phenotypes associated with different cytokine profiles. Methods Serum levels of 34 cytokines were prospectively measured in 47 consecutive DM patients and healthy controls. Concentrations of the cytokines were compared between the active and stable groups. Univariate and multivariate logistic regression models were used to identify the cytokines associated with DM disease activity. The cytokine profiles of anti-MDA5 and anti-TIF1γ subsets were compared, and the correlation analysis was performed between the elevated cytokines and clinical parameters in the two subsets. Hierarchical cluster analysis was used to establish clinical-cytokine subgroups in DM. Results Serum levels of MIP-1α, IP-10, IL-8, IL-1RA, MCP-1, GRO-α, and IL-22 were significantly higher in DM patients compared with healthy controls. IP-10, IL-6, IL-1RA, IFN-α, and MCP-1 were significantly elevated in the DM-active subset than the DM-stable subset. The combination of three cytokines (IP-10, IL-1RA, and MCP-1) had a better performance in differentiating between the active subset and the stable subset than the conventional inflammatory markers. SDF-1α, IP-10, IL-7, IL-17A, RANTES, IFN-γ, TNF-α, MIP-1β, IFN-α, MCP-1, GRO-α, and IL-1α were significantly higher in the anti-MDA5 subset than in the TIF1γ subset. Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM. Conclusions Multiple cytokine signatures were depicted in different subsets of DM. A vasculitis-associated subgroup was firstly identified in DM with regards of cytokinome and deserves further mechanistic study. Key Points • The multivariate regression model of three cytokines (IP-10 , IL-1RA , and MCP-1) could be a promising tool for distinguishing between the active and stable subset in DM. • Cytokine profiles of anti-MDA5-DM and anti-TIF1γ-DM were compared to identify the immunopathological differences between the two subsets. • Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.
AbstractList Objectives Dermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference in cytokine profiles of different subsets in DM based on the disease activity and myositis-specific antibodies, and to identify the clinical phenotypes associated with different cytokine profiles. Methods Serum levels of 34 cytokines were prospectively measured in 47 consecutive DM patients and healthy controls. Concentrations of the cytokines were compared between the active and stable groups. Univariate and multivariate logistic regression models were used to identify the cytokines associated with DM disease activity. The cytokine profiles of anti-MDA5 and anti-TIF1γ subsets were compared, and the correlation analysis was performed between the elevated cytokines and clinical parameters in the two subsets. Hierarchical cluster analysis was used to establish clinical-cytokine subgroups in DM. Results Serum levels of MIP-1α, IP-10, IL-8, IL-1RA, MCP-1, GRO-α, and IL-22 were significantly higher in DM patients compared with healthy controls. IP-10, IL-6, IL-1RA, IFN-α, and MCP-1 were significantly elevated in the DM-active subset than the DM-stable subset. The combination of three cytokines (IP-10, IL-1RA, and MCP-1) had a better performance in differentiating between the active subset and the stable subset than the conventional inflammatory markers. SDF-1α, IP-10, IL-7, IL-17A, RANTES, IFN-γ, TNF-α, MIP-1β, IFN-α, MCP-1, GRO-α, and IL-1α were significantly higher in the anti-MDA5 subset than in the TIF1γ subset. Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM. Conclusions Multiple cytokine signatures were depicted in different subsets of DM. A vasculitis-associated subgroup was firstly identified in DM with regards of cytokinome and deserves further mechanistic study. Key Points • The multivariate regression model of three cytokines (IP-10 , IL-1RA , and MCP-1) could be a promising tool for distinguishing between the active and stable subset in DM. • Cytokine profiles of anti-MDA5-DM and anti-TIF1γ-DM were compared to identify the immunopathological differences between the two subsets. • Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.
ObjectivesDermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference in cytokine profiles of different subsets in DM based on the disease activity and myositis-specific antibodies, and to identify the clinical phenotypes associated with different cytokine profiles.MethodsSerum levels of 34 cytokines were prospectively measured in 47 consecutive DM patients and healthy controls. Concentrations of the cytokines were compared between the active and stable groups. Univariate and multivariate logistic regression models were used to identify the cytokines associated with DM disease activity. The cytokine profiles of anti-MDA5 and anti-TIF1γ subsets were compared, and the correlation analysis was performed between the elevated cytokines and clinical parameters in the two subsets. Hierarchical cluster analysis was used to establish clinical-cytokine subgroups in DM.ResultsSerum levels of MIP-1α, IP-10, IL-8, IL-1RA, MCP-1, GRO-α, and IL-22 were significantly higher in DM patients compared with healthy controls. IP-10, IL-6, IL-1RA, IFN-α, and MCP-1 were significantly elevated in the DM-active subset than the DM-stable subset. The combination of three cytokines (IP-10, IL-1RA, and MCP-1) had a better performance in differentiating between the active subset and the stable subset than the conventional inflammatory markers. SDF-1α, IP-10, IL-7, IL-17A, RANTES, IFN-γ, TNF-α, MIP-1β, IFN-α, MCP-1, GRO-α, and IL-1α were significantly higher in the anti-MDA5 subset than in the TIF1γ subset. Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.ConclusionsMultiple cytokine signatures were depicted in different subsets of DM. A vasculitis-associated subgroup was firstly identified in DM with regards of cytokinome and deserves further mechanistic study.Key Points• The multivariate regression model of three cytokines (IP-10, IL-1RA, and MCP-1) could be a promising tool for distinguishing between the active and stable subset in DM.• Cytokine profiles of anti-MDA5-DM and anti-TIF1γ-DM were compared to identify the immunopathological differences between the two subsets.• Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.
Dermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference in cytokine profiles of different subsets in DM based on the disease activity and myositis-specific antibodies, and to identify the clinical phenotypes associated with different cytokine profiles.OBJECTIVESDermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference in cytokine profiles of different subsets in DM based on the disease activity and myositis-specific antibodies, and to identify the clinical phenotypes associated with different cytokine profiles.Serum levels of 34 cytokines were prospectively measured in 47 consecutive DM patients and healthy controls. Concentrations of the cytokines were compared between the active and stable groups. Univariate and multivariate logistic regression models were used to identify the cytokines associated with DM disease activity. The cytokine profiles of anti-MDA5 and anti-TIF1γ subsets were compared, and the correlation analysis was performed between the elevated cytokines and clinical parameters in the two subsets. Hierarchical cluster analysis was used to establish clinical-cytokine subgroups in DM.METHODSSerum levels of 34 cytokines were prospectively measured in 47 consecutive DM patients and healthy controls. Concentrations of the cytokines were compared between the active and stable groups. Univariate and multivariate logistic regression models were used to identify the cytokines associated with DM disease activity. The cytokine profiles of anti-MDA5 and anti-TIF1γ subsets were compared, and the correlation analysis was performed between the elevated cytokines and clinical parameters in the two subsets. Hierarchical cluster analysis was used to establish clinical-cytokine subgroups in DM.Serum levels of MIP-1α, IP-10, IL-8, IL-1RA, MCP-1, GRO-α, and IL-22 were significantly higher in DM patients compared with healthy controls. IP-10, IL-6, IL-1RA, IFN-α, and MCP-1 were significantly elevated in the DM-active subset than the DM-stable subset. The combination of three cytokines (IP-10, IL-1RA, and MCP-1) had a better performance in differentiating between the active subset and the stable subset than the conventional inflammatory markers. SDF-1α, IP-10, IL-7, IL-17A, RANTES, IFN-γ, TNF-α, MIP-1β, IFN-α, MCP-1, GRO-α, and IL-1α were significantly higher in the anti-MDA5 subset than in the TIF1γ subset. Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.RESULTSSerum levels of MIP-1α, IP-10, IL-8, IL-1RA, MCP-1, GRO-α, and IL-22 were significantly higher in DM patients compared with healthy controls. IP-10, IL-6, IL-1RA, IFN-α, and MCP-1 were significantly elevated in the DM-active subset than the DM-stable subset. The combination of three cytokines (IP-10, IL-1RA, and MCP-1) had a better performance in differentiating between the active subset and the stable subset than the conventional inflammatory markers. SDF-1α, IP-10, IL-7, IL-17A, RANTES, IFN-γ, TNF-α, MIP-1β, IFN-α, MCP-1, GRO-α, and IL-1α were significantly higher in the anti-MDA5 subset than in the TIF1γ subset. Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.Multiple cytokine signatures were depicted in different subsets of DM. A vasculitis-associated subgroup was firstly identified in DM with regards of cytokinome and deserves further mechanistic study. Key Points • The multivariate regression model of three cytokines (IP-10, IL-1RA, and MCP-1) could be a promising tool for distinguishing between the active and stable subset in DM. • Cytokine profiles of anti-MDA5-DM and anti-TIF1γ-DM were compared to identify the immunopathological differences between the two subsets. • Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.CONCLUSIONSMultiple cytokine signatures were depicted in different subsets of DM. A vasculitis-associated subgroup was firstly identified in DM with regards of cytokinome and deserves further mechanistic study. Key Points • The multivariate regression model of three cytokines (IP-10, IL-1RA, and MCP-1) could be a promising tool for distinguishing between the active and stable subset in DM. • Cytokine profiles of anti-MDA5-DM and anti-TIF1γ-DM were compared to identify the immunopathological differences between the two subsets. • Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.
Dermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference in cytokine profiles of different subsets in DM based on the disease activity and myositis-specific antibodies, and to identify the clinical phenotypes associated with different cytokine profiles. Serum levels of 34 cytokines were prospectively measured in 47 consecutive DM patients and healthy controls. Concentrations of the cytokines were compared between the active and stable groups. Univariate and multivariate logistic regression models were used to identify the cytokines associated with DM disease activity. The cytokine profiles of anti-MDA5 and anti-TIF1γ subsets were compared, and the correlation analysis was performed between the elevated cytokines and clinical parameters in the two subsets. Hierarchical cluster analysis was used to establish clinical-cytokine subgroups in DM. Serum levels of MIP-1α, IP-10, IL-8, IL-1RA, MCP-1, GRO-α, and IL-22 were significantly higher in DM patients compared with healthy controls. IP-10, IL-6, IL-1RA, IFN-α, and MCP-1 were significantly elevated in the DM-active subset than the DM-stable subset. The combination of three cytokines (IP-10, IL-1RA, and MCP-1) had a better performance in differentiating between the active subset and the stable subset than the conventional inflammatory markers. SDF-1α, IP-10, IL-7, IL-17A, RANTES, IFN-γ, TNF-α, MIP-1β, IFN-α, MCP-1, GRO-α, and IL-1α were significantly higher in the anti-MDA5 subset than in the TIF1γ subset. Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM. Multiple cytokine signatures were depicted in different subsets of DM. A vasculitis-associated subgroup was firstly identified in DM with regards of cytokinome and deserves further mechanistic study. Key Points • The multivariate regression model of three cytokines (IP-10, IL-1RA, and MCP-1) could be a promising tool for distinguishing between the active and stable subset in DM. • Cytokine profiles of anti-MDA5-DM and anti-TIF1γ-DM were compared to identify the immunopathological differences between the two subsets. • Cluster analysis revealed a hypercytokinemic-vasculitis subgroup in patients with DM.
Author Wu, Chanyuan
Wang, Qian
Xu, Dong
Zhong, Danli
Bai, Jingjing
Zeng, Xiaofeng
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  organization: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID)
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32797361$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright International League of Associations for Rheumatology (ILAR) 2020
International League of Associations for Rheumatology (ILAR) 2020.
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Thu Apr 24 23:13:04 EDT 2025
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Keywords Cluster analysis
Cutaneous vasculitis
Cytokine
Dermatomyositis
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PublicationSubtitle Journal of the International League of Associations for Rheumatology
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– volume: 39
  start-page: 128
  issue: 2
  year: 2000
  ident: 5339_CR25
  publication-title: Intern Med
  doi: 10.2169/internalmedicine.39.128
– volume: 292
  start-page: 344
  issue: 7
  year: 1975
  ident: 5339_CR12
  publication-title: N Engl J Med
  doi: 10.1056/nejm197502132920706
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Snippet Objectives Dermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference...
Dermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference in...
ObjectivesDermatomyositis (DM) is a chronic inflammatory autoimmune disease with notable heterogeneity. The intent of this study was to explore the difference...
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SubjectTerms Autoimmune diseases
Cluster Analysis
Correlation analysis
Cytokines
Dermatomyositis
Dermatomyositis - complications
Humans
Interleukin 1 receptor antagonist
Interleukin 1 receptors
Interleukin 22
Interleukin 6
Interleukin 7
Interleukin 8
IP-10 protein
Medicine
Medicine & Public Health
Monocyte chemoattractant protein 1
Myositis
Original Article
Phenotypes
RANTES
Regression analysis
Rheumatology
Serum levels
Tumor Necrosis Factor-alpha
Tumor necrosis factor-α
Vasculitis
α-Interferon
γ-Interferon
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Title Hierarchical cluster analysis of cytokine profiles reveals a cutaneous vasculitis-associated subgroup in dermatomyositis
URI https://link.springer.com/article/10.1007/s10067-020-05339-2
https://www.ncbi.nlm.nih.gov/pubmed/32797361
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