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Pityriasis rubra pilaris transcriptomics implicate Th17 signaling and correlate with response to ixekizumab, with distinct gene expression profiles in non-responders

Published:September 24, 2022DOI:https://doi.org/10.1016/j.jid.2022.09.005
      Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder associated with significant patient morbidity (
      • Eastham A.B.
      • Tkachenko E.Y.
      • Femia A.N.
      • Pappas-Taffer L.K.
      • Rosenbach M.
      • Joyce C.J.
      • et al.
      Pityriasis rubra pilaris: A study evaluating patient quality of life in 2 populations.
      ,
      • Ji-Xu A.
      • Lei D.K.
      • Worswick S.
      • Maloney N.J.
      • Kim M.M.
      • Cutler L.
      Patient and disease characteristics associated with psychiatric symptoms and impaired quality of life in pityriasis rubra pilaris.
      ). Recent discoveries in the pathophysiology of PRP—including alterations in IL17 signaling (
      • Feldmeyer L.
      • Mylonas A.
      • Demaria O.
      • Mennella A.
      • Yawalkar N.
      • Laffitte E.
      • et al.
      Interleukin 23–Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris.
      ,
      • Haynes D.
      • Strunck J.L.
      • Topham C.A.
      • Ortega-Loayza A.G.
      • Kent G.
      • Cassidy P.B.
      • et al.
      Evaluation of Ixekizumab Treatment for Patients With Pityriasis Rubra Pilaris: A Single-Arm Trial.
      ,
      • Strunck J.L.
      • Cutler B.
      • Rajpal B.
      • Kent G.
      • Haynes D.
      • Topham C.A.
      • et al.
      Pityriasis Rubra Pilaris Response to IL-17A Inhibition Is Associated with IL-17C and CCL20 Protein Levels.
      ,
      • Boudreaux B.W.
      • Pincelli T.P.
      • Bhullar P.K.
      • Patel M.H.
      • Brumfiel C.M.
      • Li X.
      • Heckman M.G.
      • Pittelkow M.R.
      • Mangold A.R.
      • Sluzevich J.C.
      Secukinumab for the treatment of adult-onset pityriasis rubra pilaris: a single-arm clinical trial with transcriptomic analysis.
      ), phospholipase A2 processing (
      • Shao S.
      • Chen J.
      • Swindell W.R.
      • Tsoi L.C.
      • Xing X.
      • Ma F.
      • et al.
      Phospholipase A2 enzymes represent a shared pathogenic pathway in psoriasis and pityriasis rubra pilaris.
      ), and novel germline CARD14 genetic variations (
      • Fuchs-Telem D.
      • Sarig O.
      • van Steensel M.A.
      • Isakov O.
      • Israeli S.
      • Nousbeck J.
      • et al.
      Familial pityriasis rubra pilaris is caused by mutations in CARD14.
      )—have yielded new diagnostic and therapeutic insights. To further characterize the molecular landscape of PRP, we conducted a transcriptomic analysis of epidermis and dermis collected from PRP patients on no systemic therapy and then following 24 weeks of treatment with the IL17A inhibitor, ixekizumab (
      • Haynes D.
      • Strunck J.L.
      • Topham C.A.
      • Ortega-Loayza A.G.
      • Kent G.
      • Cassidy P.B.
      • et al.
      Evaluation of Ixekizumab Treatment for Patients With Pityriasis Rubra Pilaris: A Single-Arm Trial.
      ) compared to matched healthy controls.

      Abbreviations:

      DEG (Differentially Expressed Gene), GO (Gene Ontology), Log2FC (Log2 Fold Change), PASI (Psoriasis Area and Severity Index), PRP (Pityriasis rubra pilaris)
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