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 in | Clinical rheumatology Vol. 40; no. 3; pp. 999 - 1008 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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. |
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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 |
Author_xml | – sequence: 1 givenname: Jingjing surname: Bai fullname: Bai, Jingjing 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) – sequence: 2 givenname: Chanyuan surname: Wu fullname: Wu, Chanyuan 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) – sequence: 3 givenname: Danli surname: Zhong fullname: Zhong, Danli 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) – sequence: 4 givenname: Dong surname: Xu fullname: Xu, Dong 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) – sequence: 5 givenname: Qian orcidid: 0000-0002-4541-9898 surname: Wang fullname: Wang, Qian email: wangqian_pumch@126.com 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) – sequence: 6 givenname: Xiaofeng surname: Zeng fullname: Zeng, Xiaofeng email: xiaofeng.zeng@cstar.org.cn 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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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 |
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