Gene expression profiling in blood and affected muscle tissues reveals differential activation pathways in patients with new-onset juvenile and adult dermatomyositis

Consuelo M. Lopez De Padilla, Cynthia Crowson, Molly S. Hein, Richard S. Pendegraft, Michael A. Strausbauch, Timothy B. Niewold, Floranne C. Ernste, Erik Peterson, Emily C. Baechler, Ann M. Reed

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective. To identify shared and differential molecular pathways in blood and affected muscle between adult dermatomyositis (DM) and juvenile DM, and their association with clinical disease activity measures. Methods. Gene expression of transcription factors and cytokines involved in differentiation and effector function of T cell subsets, regulatory T cells and follicular Th cells, were analyzed in the blood from 21 newly diagnosed adult and 26 juvenile DM subjects and in 15 muscle specimens (7 adult and 8 juvenile DM) using a custom RT2 Profiler PCR Array. Disease activity was determined and measured by established disease activity tools. Results. The most prominent finding was the higher blood expression of Th17-related cytokines [retinoic acid-related orphan receptor-γ, interferon regulatory factor 4, interleukin (IL)-23A, IL-6, IL-17F, and IL-21] in juvenile DM at baseline. In contrast, adult patients with DM showed increased blood levels of STAT3 and BCL6 compared with juvenile DM. In muscle, GATA3, IL-13, and STAT5B were found at higher levels in juvenile patients with DM compared with adult DM. Among 25 patients (11 adult and 14 juvenile DM) who had blood samples at baseline and at 6 months, increased expression of IL-1β, STAT3, STAT6, STAT5B, and BCL6 was associated with an improvement in global extramuscular disease activity. Conclusion. We observed differences in gene expression profiling in blood and muscle between new-onset adult and juvenile DM. Cytokine expression in the blood of juvenile patients with new-onset DM was dominated by Th17-related cytokines compared with adult patients with DM. This may reflect the activation of different Th pathways between muscle and blood.

Original languageEnglish (US)
Pages (from-to)117-124
Number of pages8
JournalJournal of Rheumatology
Volume44
Issue number1
DOIs
StatePublished - Jan 1 2017

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Gene Expression Profiling
Dermatomyositis
Muscles
Cytokines
Interleukin-13
Interleukin-17
Juvenile dermatomyositis
Interleukins
T-Lymphocyte Subsets
Regulatory T-Lymphocytes
Tretinoin
Interleukin-1
Interleukin-6
Transcription Factors
Gene Expression
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Gene expression profiling in blood and affected muscle tissues reveals differential activation pathways in patients with new-onset juvenile and adult dermatomyositis. / Lopez De Padilla, Consuelo M.; Crowson, Cynthia; Hein, Molly S.; Pendegraft, Richard S.; Strausbauch, Michael A.; Niewold, Timothy B.; Ernste, Floranne C.; Peterson, Erik; Baechler, Emily C.; Reed, Ann M.

In: Journal of Rheumatology, Vol. 44, No. 1, 01.01.2017, p. 117-124.

Research output: Contribution to journalArticle

Lopez De Padilla, CM, Crowson, C, Hein, MS, Pendegraft, RS, Strausbauch, MA, Niewold, TB, Ernste, FC, Peterson, E, Baechler, EC & Reed, AM 2017, 'Gene expression profiling in blood and affected muscle tissues reveals differential activation pathways in patients with new-onset juvenile and adult dermatomyositis', Journal of Rheumatology, vol. 44, no. 1, pp. 117-124. https://doi.org/10.3899/jrheum.160293
Lopez De Padilla, Consuelo M. ; Crowson, Cynthia ; Hein, Molly S. ; Pendegraft, Richard S. ; Strausbauch, Michael A. ; Niewold, Timothy B. ; Ernste, Floranne C. ; Peterson, Erik ; Baechler, Emily C. ; Reed, Ann M. / Gene expression profiling in blood and affected muscle tissues reveals differential activation pathways in patients with new-onset juvenile and adult dermatomyositis. In: Journal of Rheumatology. 2017 ; Vol. 44, No. 1. pp. 117-124.
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abstract = "Objective. To identify shared and differential molecular pathways in blood and affected muscle between adult dermatomyositis (DM) and juvenile DM, and their association with clinical disease activity measures. Methods. Gene expression of transcription factors and cytokines involved in differentiation and effector function of T cell subsets, regulatory T cells and follicular Th cells, were analyzed in the blood from 21 newly diagnosed adult and 26 juvenile DM subjects and in 15 muscle specimens (7 adult and 8 juvenile DM) using a custom RT2 Profiler PCR Array. Disease activity was determined and measured by established disease activity tools. Results. The most prominent finding was the higher blood expression of Th17-related cytokines [retinoic acid-related orphan receptor-γ, interferon regulatory factor 4, interleukin (IL)-23A, IL-6, IL-17F, and IL-21] in juvenile DM at baseline. In contrast, adult patients with DM showed increased blood levels of STAT3 and BCL6 compared with juvenile DM. In muscle, GATA3, IL-13, and STAT5B were found at higher levels in juvenile patients with DM compared with adult DM. Among 25 patients (11 adult and 14 juvenile DM) who had blood samples at baseline and at 6 months, increased expression of IL-1β, STAT3, STAT6, STAT5B, and BCL6 was associated with an improvement in global extramuscular disease activity. Conclusion. We observed differences in gene expression profiling in blood and muscle between new-onset adult and juvenile DM. Cytokine expression in the blood of juvenile patients with new-onset DM was dominated by Th17-related cytokines compared with adult patients with DM. This may reflect the activation of different Th pathways between muscle and blood.",
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AU - Lopez De Padilla, Consuelo M.

AU - Crowson, Cynthia

AU - Hein, Molly S.

AU - Pendegraft, Richard S.

AU - Strausbauch, Michael A.

AU - Niewold, Timothy B.

AU - Ernste, Floranne C.

AU - Peterson, Erik

AU - Baechler, Emily C.

AU - Reed, Ann M.

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N2 - Objective. To identify shared and differential molecular pathways in blood and affected muscle between adult dermatomyositis (DM) and juvenile DM, and their association with clinical disease activity measures. Methods. Gene expression of transcription factors and cytokines involved in differentiation and effector function of T cell subsets, regulatory T cells and follicular Th cells, were analyzed in the blood from 21 newly diagnosed adult and 26 juvenile DM subjects and in 15 muscle specimens (7 adult and 8 juvenile DM) using a custom RT2 Profiler PCR Array. Disease activity was determined and measured by established disease activity tools. Results. The most prominent finding was the higher blood expression of Th17-related cytokines [retinoic acid-related orphan receptor-γ, interferon regulatory factor 4, interleukin (IL)-23A, IL-6, IL-17F, and IL-21] in juvenile DM at baseline. In contrast, adult patients with DM showed increased blood levels of STAT3 and BCL6 compared with juvenile DM. In muscle, GATA3, IL-13, and STAT5B were found at higher levels in juvenile patients with DM compared with adult DM. Among 25 patients (11 adult and 14 juvenile DM) who had blood samples at baseline and at 6 months, increased expression of IL-1β, STAT3, STAT6, STAT5B, and BCL6 was associated with an improvement in global extramuscular disease activity. Conclusion. We observed differences in gene expression profiling in blood and muscle between new-onset adult and juvenile DM. Cytokine expression in the blood of juvenile patients with new-onset DM was dominated by Th17-related cytokines compared with adult patients with DM. This may reflect the activation of different Th pathways between muscle and blood.

AB - Objective. To identify shared and differential molecular pathways in blood and affected muscle between adult dermatomyositis (DM) and juvenile DM, and their association with clinical disease activity measures. Methods. Gene expression of transcription factors and cytokines involved in differentiation and effector function of T cell subsets, regulatory T cells and follicular Th cells, were analyzed in the blood from 21 newly diagnosed adult and 26 juvenile DM subjects and in 15 muscle specimens (7 adult and 8 juvenile DM) using a custom RT2 Profiler PCR Array. Disease activity was determined and measured by established disease activity tools. Results. The most prominent finding was the higher blood expression of Th17-related cytokines [retinoic acid-related orphan receptor-γ, interferon regulatory factor 4, interleukin (IL)-23A, IL-6, IL-17F, and IL-21] in juvenile DM at baseline. In contrast, adult patients with DM showed increased blood levels of STAT3 and BCL6 compared with juvenile DM. In muscle, GATA3, IL-13, and STAT5B were found at higher levels in juvenile patients with DM compared with adult DM. Among 25 patients (11 adult and 14 juvenile DM) who had blood samples at baseline and at 6 months, increased expression of IL-1β, STAT3, STAT6, STAT5B, and BCL6 was associated with an improvement in global extramuscular disease activity. Conclusion. We observed differences in gene expression profiling in blood and muscle between new-onset adult and juvenile DM. Cytokine expression in the blood of juvenile patients with new-onset DM was dominated by Th17-related cytokines compared with adult patients with DM. This may reflect the activation of different Th pathways between muscle and blood.

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