title: Ustekinumab improves psoriasis-related gene expression in noninvolved psoriatic skin without inhibition of the antimicrobial response.
abstract: BACKGROUND
  Ustekinumab is a fully human anti-p40 monoclonal antibody which neutralizes interleukin (IL)-12 and IL-23, thereby interfering with T-helper (Th)1/Th17 pathways and keratinocyte activation, and is highly effective in the treatment of psoriasis. During ustekinumab treatment, some of our patients noticed reduced koebnerization of noninvolved skin and less new plaque formation.
  
  
  OBJECTIVE
  To determine whether ustekinumab improves psoriasis-related gene expression and tape-strip responses in noninvolved skin.
  
  
  METHODS
  Before and 4 weeks after ustekinumab treatment, noninvolved skin was tape-stripped. After 5 h, biopsies were taken from untouched and tape-stripped skin. The mRNA expression of psoriasis-related markers such as NGF, GATA3 and IL-22RA1, and several antimicrobial peptides (AMP) was quantified. Leucocyte counts and a broad range of inflammatory serum proteins were analysed to gain insight into the systemic alterations.
  
  
  RESULTS
  Four weeks following a single ustekinumab injection, NGF showed a significant decrease, whereas GATA3 and IL-22RA1 expression increased, indicative of reduced responsiveness to epidermal triggering. This was accompanied by an increase of the inflammation-related serum proteins GPNMB, MST1 and TRADD. The baseline and tape-strip-induced mRNA expression of the AMP human β-defensin-2 (hBD-2), S100A7 and LL-37 remained unaltered. Clinically, after 4 weeks, eight out of 11 patients showed a 50% psoriasis area and severity index (PASI) improvement, which was accompanied by a significant reduction in serum hBD-2 levels. No changes were noted in total leucocytes, C-reactive protein and erythrocyte sedimentation rate.
  
  
  CONCLUSIONS
  These findings indicate that ustekinumab reduces psoriasis-related gene expression in noninvolved psoriatic skin, making it more resistant to exogenous triggering, without disturbing its antimicrobial response. In parallel, ustekinumab modulates important circulating inflammation-related proteins.
authors.affiliation: Department of Dermatology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, the Netherlands. e.baerveldt@erasmusmc.nl
authors.forename: E M
authors.initials: EM
authors.lastname: Baerveldt
authors.forename: A J
authors.initials: AJ
authors.lastname: Onderdijk
authors.forename: D
authors.initials: D
authors.lastname: Kurek
authors.forename: M
authors.initials: M
authors.lastname: Kant
authors.forename: E F
authors.initials: EF
authors.lastname: Florencia
authors.forename: A S
authors.initials: AS
authors.lastname: Ijpma
authors.forename: P J
authors.initials: PJ
authors.lastname: van der Spek
authors.forename: J
authors.initials: J
authors.lastname: Bastiaans
authors.forename: P A
authors.initials: PA
authors.lastname: Jansen
authors.forename: J W J
authors.initials: JW
authors.lastname: van Kilsdonk
authors.forename: J D
authors.initials: JD
authors.lastname: Laman
authors.forename: E P
authors.initials: EP
authors.lastname: Prens
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D003879:Dermatologic Agents / Q000627:therapeutic use*; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000235:genetics*; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics*; D012720:Severity of Illness Index; D012867:Skin / Q000187:drug effects; D016896:Treatment Outcome; D000069549:Ustekinumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D023181:Antimicrobial Cationic Peptides; D003879:Dermatologic Agents; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D053759:Interleukin-23; C502240:NGF protein, human; D012333:RNA, Messenger; D018123:Receptors, Interleukin; C415369:interleukin-22 receptor; D018664:Interleukin-12; D020932:Nerve Growth Factor; D000069549:Ustekinumab