Advertisement
Journal of Investigative Dermatology Home

Molecular and Cellular Characterization of Pyoderma Gangrenosum: Implications for the Use of Gene Expression

Published:September 15, 2021DOI:https://doi.org/10.1016/j.jid.2021.08.431
      Pyoderma gangrenosum (PG) is characterized by painful ulcers typically affecting the lower extremities. PG pathogenesis and triggers are poorly understood (
      • Ortega-Loayza A.G.
      • Nugent W.H.
      • Lucero O.M.
      • Washington S.L.
      • Nunley J.R.
      • Walsh S.W.
      Dysregulation of inflammatory gene expression in lesional and nonlesional skin of patients with pyoderma gangrenosum.
      ). Treatments target systemic inflammation, but clinical response and outcomes remain unpredictable. Further investigations are necessary to understand PG pathobiology; however, little is known about gene expression in PG, including whether important changes localize to the dermis or epidermis and whether nonlesional skin from patients with PG shows subclinical signs of the disease. Thus, we analyzed the gene expression signatures of perilesional and nonlesional skin biopsies from patients with PG to characterize the immunologic and cellular response. This study was approved by Oregon Health and Science University’s Institutional Review Board.

      Abbreviations:

      DPPG (dermis perilesional pyoderma gangrenosum), HC (healthy control), PG (pyoderma gangrenosum)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      PDF Download and 24 Hours Online Access
      Society Members (SID/ESDR), remember to log in for access.

      Subscribe:

      Subscribe to Journal of Investigative Dermatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Benjamini Y.
        • Hochberg Y.
        Controlling the false discovery rate: a practical and powerful approach to multiple testing.
        J R Stat Soc Series B Stat Methodol. 1995; 57: 289-300
        • Chu C.C.
        • Di Meglio P.
        • Nestle F.O.
        Harnessing dendritic cells in inflammatory skin diseases.
        Semin Immunol. 2011; 23: 28-41
        • Clemmensen A.
        • Thomassen M.
        • Clemmensen O.
        • Tan Q.
        • Kruse T.A.
        • Petersen T.K.
        • et al.
        Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo-epidermal separation of 4 mm human skin biopsies.
        Exp Dermatol. 2009; 18: 979-984
        • Dobin A.
        • Davis C.A.
        • Schlesinger F.
        • Drenkow J.
        • Zaleski C.
        • Jha S.
        • et al.
        STAR: ultrafast universal RNA-seq aligner.
        Bioinformatics. 2013; 29: 15-21
        • Heng T.S.
        • Painter M.W.
        Immunological Genome Project Consortium. The immunological Genome Project: networks of gene expression in immune cells.
        Nat Immunol. 2008; 9: 1091-1094
        • Orfaly V.E.
        • Kovalenko I.
        • Tolkachjov S.N.
        • Ortega-Loayza A.G.
        • Nunley J.R.
        Tofacitinib for the treatment of refractory pyoderma gangrenosum.
        Clin Exp Dermatol. 2021; 46: 1082-1085
        • Ortega-Loayza A.G.
        • Nugent W.H.
        • Lucero O.M.
        • Washington S.L.
        • Nunley J.R.
        • Walsh S.W.
        Dysregulation of inflammatory gene expression in lesional and nonlesional skin of patients with pyoderma gangrenosum.
        Br J Dermatol. 2018; 178: e35-e36
        • Ritchie M.E.
        • Phipson B.
        • Wu D.
        • Hu Y.
        • Law C.W.
        • Shi W.
        • et al.
        limma powers differential expression analyses for RNA-sequencing and microarray studies.
        Nucleic Acids Res. 2015; 43: e47
        • Shannon P.
        • Markiel A.
        • Ozier O.
        • Baliga N.S.
        • Wang J.T.
        • Ramage D.
        • et al.
        Cytoscape: a software environment for integrated models of biomolecular interaction networks.
        Genome Res. 2003; 13: 2498-2504
        • Wang E.A.
        • Steel A.
        • Luxardi G.
        • Mitra A.
        • Patel F.
        • Cheng M.Y.
        • et al.
        Classic ulcerative pyoderma gangrenosum is a T cell-mediated disease targeting follicular adnexal structures: a hypothesis based on molecular and clinicopathologic studies.
        Front Immunol. 2018; 8: 1980
        • Weedon D.
        The vasculopathic reaction pattern.
        in: Weedon D. Weedon’s skin pathology. 3rd ed. Elsevier Churchill Livingstone, London, United Kingdom2010: 195

      Supplementary References

        • Benjamini Y.
        • Hochberg Y.
        Controlling the false discovery rate: a practical and powerful approach to multiple testing.
        J R Stat Soc Series B Stat Methodol. 1995; 57: 289-300
        • Chen Y.
        • Lun A.T.
        • Smyth G.K.
        From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline.
        F1000Res. 2016; : 1438
        • Fabregat A.
        • Jupe S.
        • Matthews L.
        • Sidiropoulous K.
        • Gillespie M.
        • Garapati P.
        • et al.
        The reactome pathways knowledge base.
        Nucleic Acids Res. 2018; 46: D649-D655
        • Law C.W.
        • Chen Y.
        • Shi W.
        • Smyth G.K.
        voom: Precision weights unlock linear model analysis tools for RNA-seq read counts.
        Genome Biol. 2014; 15: R29
        • Reactome
        ReactomeRIVIz.
        (accessed 4 February 2018)
        • Robinson M.D.
        • Oshlack A.
        A scaling normalization method for differential expression analysis of RNA-seq data.
        Genome Biol. 2010; 11: R25
        • Shannon P.
        • Markiel A.
        • Ozier O.
        • Baliga N.S.
        • Wang J.T.
        • Ramage D.
        • et al.
        Cytoscape: A softward environment for integrated models of biomolecular interaction networks.
        Genome Res. 2003; 13: 2498-2504
        • Su W.P.
        • Davis M.D.
        • Weenig R.H.
        • Powell F.C.
        • Perry H.O.
        Pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria.
        Int J Dermatol. 2004; 43: 790-800