Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile.

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  • Additional Information
    • Affiliation:
      Division of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, USA
      Scleroderma Program, Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA
      Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio, USA
      Department of Internal Medicine, The Jewish Hospital, Cincinnati, Ohio, USA
      Department of Medicine, Section of Allergy, Rheumatology, and Immunology, Yale University, New Haven, Connecticut, USA
      Division of Rheumatology, Department of Internal Medicine, University of Utah and Salt Lake Regional Veterans Affairs Medical Center, Salt Lake City, Utah, USA
      Division of Rheumatology, Department of Medicine, MedStar Georgetown University Hospital, Washington, DC, USA
      Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
      Department of Rheumatology, Hospital for Special Surgery, New York City, New York, USA
      Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
      School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, Texas, USA
      Department of Microbiology, Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts, USA
      Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA
      Boehringer Ingelheim International GmbH, Biberach, Germany
      Department of Biomedical Data Science, Dartmouth College Geisel School of Medicine, Lebanon, New Hampshire, USA
      Department of Molecular and Systems Biology, Dartmouth College Geisel School of Medicine, Hanover, New Hampshire, USA
      Division of Rheumatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
      Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    • Subject Terms:
    • Subject Terms:
    • Abstract:
      Objectives: Determine global skin transcriptome patterns of early diffuse systemic sclerosis (SSc) and how they differ from later disease.Methods: Skin biopsy RNA from 48 patients in the Prospective Registry for Early Systemic Sclerosis (PRESS) cohort (mean disease duration 1.3 years) and 33 matched healthy controls was examined by next-generation RNA sequencing. Data were analysed for cell type-specific signatures and compared with similarly obtained data from 55 previously biopsied patients in Genetics versus Environment in Scleroderma Outcomes Study cohort with longer disease duration (mean 7.4 years) and their matched controls. Correlations with histological features and clinical course were also evaluated.Results: SSc patients in PRESS had a high prevalence of M2 (96%) and M1 (94%) macrophage and CD8 T cell (65%), CD4 T cell (60%) and B cell (69%) signatures. Immunohistochemical staining of immune cell markers correlated with the gene expression-based immune cell signatures. The prevalence of immune cell signatures in early diffuse SSc patients was higher than in patients with longer disease duration. In the multivariable model, adaptive immune cell signatures were significantly associated with shorter disease duration, while fibroblast and macrophage cell type signatures were associated with higher modified Rodnan Skin Score (mRSS). Immune cell signatures also correlated with skin thickness progression rate prior to biopsy, but did not predict subsequent mRSS progression.Conclusions: Skin in early diffuse SSc has prominent innate and adaptive immune cell signatures. As a prominently affected end organ, these signatures reflect the preceding rate of disease progression. These findings could have implications in understanding SSc pathogenesis and clinical trial design.
    • Journal Subset:
      Biomedical; Europe; UK & Ireland
    • Instrumentation:
      Profile of Mood States (POMS)
      Clinical Decision Making in Nursing Scale (CDMNS) (Jenkins)
      Global Assessment of Functioning Scale (GAF)
      Somatic Symptom Checklist
    • ISSN:
      0003-4967
    • MEDLINE Info:
      PMID: NLM31767698 NLM UID: 0372355
    • Grant Information:
      UL1 TR003167/TR/NCATS NIH HHS/United States; P50 AR060780/AR/NIAMS NIH HHS/United States; R01 AR073284/AR/NIAMS NIH HHS/United States; T32 LM012204/LM/NLM NIH HHS/United States; K23 AR075112/AR/NIAMS NIH HHS/United States; K24 AR063120/AR/NIAMS NIH HHS/United States
    • Publication Date:
      20200429
    • Publication Date:
      20200731
    • DOI:
      10.1136/annrheumdis-2019-215894
    • Accession Number:
      141714350
  • Citations
    • ABNT:
      SKAUG, B. et al. Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Annals of the Rheumatic Diseases, [s. l.], v. 79, n. 3, p. 379–386, 2020. DOI 10.1136/annrheumdis-2019-215894. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=141714350. Acesso em: 30 set. 2020.
    • AMA:
      Skaug B, Khanna D, Swindell WR, et al. Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Annals of the Rheumatic Diseases. 2020;79(3):379-386. doi:10.1136/annrheumdis-2019-215894
    • APA:
      Skaug, B., Khanna, D., Swindell, W. R., Hinchcliff, M. E., Frech, T. M., Steen, V. D., Hant, F. N., Gordon, J. K., Shah, A. A., Zhu, L., Zheng, W. J., Browning, J. L., Barron, A. M. S., Minghua Wu, Visvanathan, S., Baum, P., Franks, J. M., Whitfield, M. L., Shanmugam, V. K., & Domsic, R. T. (2020). Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Annals of the Rheumatic Diseases, 79(3), 379–386. https://doi.org/10.1136/annrheumdis-2019-215894
    • Chicago/Turabian: Author-Date:
      Skaug, Brian, Dinesh Khanna, William R. Swindell, Monique E. Hinchcliff, Tracy M. Frech, Virginia D. Steen, Faye N. Hant, et al. 2020. “Global Skin Gene Expression Analysis of Early Diffuse Cutaneous Systemic Sclerosis Shows a Prominent Innate and Adaptive Inflammatory Profile.” Annals of the Rheumatic Diseases 79 (3): 379–86. doi:10.1136/annrheumdis-2019-215894.
    • Harvard:
      Skaug, B. et al. (2020) ‘Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile’, Annals of the Rheumatic Diseases, 79(3), pp. 379–386. doi: 10.1136/annrheumdis-2019-215894.
    • Harvard: Australian:
      Skaug, B, Khanna, D, Swindell, WR, Hinchcliff, ME, Frech, TM, Steen, VD, Hant, FN, Gordon, JK, Shah, AA, Zhu, L, Zheng, WJ, Browning, JL, Barron, AMS, Minghua Wu, Visvanathan, S, Baum, P, Franks, JM, Whitfield, ML, Shanmugam, VK & Domsic, RT 2020, ‘Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile’, Annals of the Rheumatic Diseases, vol. 79, no. 3, pp. 379–386, viewed 30 September 2020, .
    • MLA:
      Skaug, Brian, et al. “Global Skin Gene Expression Analysis of Early Diffuse Cutaneous Systemic Sclerosis Shows a Prominent Innate and Adaptive Inflammatory Profile.” Annals of the Rheumatic Diseases, vol. 79, no. 3, Mar. 2020, pp. 379–386. EBSCOhost, doi:10.1136/annrheumdis-2019-215894.
    • Chicago/Turabian: Humanities:
      Skaug, Brian, Dinesh Khanna, William R. Swindell, Monique E. Hinchcliff, Tracy M. Frech, Virginia D. Steen, Faye N. Hant, et al. “Global Skin Gene Expression Analysis of Early Diffuse Cutaneous Systemic Sclerosis Shows a Prominent Innate and Adaptive Inflammatory Profile.” Annals of the Rheumatic Diseases 79, no. 3 (March 2020): 379–86. doi:10.1136/annrheumdis-2019-215894.
    • Vancouver/ICMJE:
      Skaug B, Khanna D, Swindell WR, Hinchcliff ME, Frech TM, Steen VD, et al. Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Annals of the Rheumatic Diseases [Internet]. 2020 Mar [cited 2020 Sep 30];79(3):379–86. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=141714350