Advertisement

European Journal of Dermatology

, Volume 27, Issue 6, pp 579–589 | Cite as

Characterization of skin Th17 transcriptional profiles in psoriatic patients under adalimumab biotherapy

  • Amandine Buffiere-Morgado
  • Elodie Couderc
  • Adriana Delwail
  • Laure Favot
  • Jean-François Jegou
  • Elisabeth Solau
  • Gérard Guillet
  • Jean-Claude Lecron
  • Frank MorelEmail author
Investigative report
  • 17 Downloads

Abstract

Background

In psoriasis, a specific cytokine network has been described to play a central role in the pathophysiology of the disease. Anti-cytokine therapeutic approaches have been largely developed and TNFα constitutes the main target. Adalimumab is a human anti-TNFα monoclonal antibody that has been reported to demonstrate clinical efficacy and safety, resulting in reversal of epidermal hyperplasia and cutaneous inflammation.

Objectives

We aimed to analyse changes in the skin inflammatory transcriptomic profile in psoriatic patients during adalimumabtherapy. In addition, the circulating cytokine profilewas analysed to define systemic inflammation.

Materials&methods

Eighteen patients with chronic plaque psoriasis were treated with adalimumab. After four and 16 weeks, clinical efficacy was assessed using PASI and DLQI, and skin mRNA profiles were determined and circulating cytokines quantified.

Results

We identified a rapid effect of adalimumab therapy on a large array of Th17 cytokines of the skin, which may account for the modification of keratinocyte expression profile and clinical response. In contrast, analysis of serum cytokine concentrations was uninformative, confirming the need for characterization of local cytokines in skin lesions. Finally, in non-responders, local cytokine expression was shown to be unchanged.

Conclusion

We showthat TNFα inhibition in psoriasis patients treated with adalimumab has a broad effect on the expression profile of cytokines and keratinocyte markers of skin inflammation, which may account for its clinical efficacy.

Key words

cytokine inflammation psoriasis biotherapy adalimumab 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009; 361: 496–509.CrossRefGoogle Scholar
  2. 2.
    Boniface K, Bernard FX, Garcia M, et al. IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol 2005; 174: 3695–702.CrossRefGoogle Scholar
  3. 3.
    Gottlieb AB, Chamian F, Masud S, et al. TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol 2005; 175: 2721–9.CrossRefGoogle Scholar
  4. 4.
    Chan JR, Blumenschein W, Murphy E, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med 2006; 203: 2577–87.CrossRefGoogle Scholar
  5. 5.
    Boniface K, Diveu C, Morel F, et al. Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation. J Immunol 2007; 178: 4615–22.CrossRefGoogle Scholar
  6. 6.
    Wilson NJ, Boniface K, Chan JR, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 2007; 8: 950–7.CrossRefGoogle Scholar
  7. 7.
    Zheng Y, Danilenko DM, Valdez P, et al. Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007; 445: 648–51.CrossRefGoogle Scholar
  8. 8.
    Guilloteau K, Paris I, Pedretti N, et al. Skin Inflammation induced by the synergistic action of IL-17A, IL-22, oncostatin M, IL-1alpha, and TNF-alpha recapitulates some features of psoriasis. J Immunol 2010; 184: 5256–70.CrossRefGoogle Scholar
  9. 9.
    Rabeony H, Petit-Paris I, Garnier J, et al. Inhibition of keratinocyte differentiation by the synergistic effect of IL-17A, IL-22, IL-1alpha, TNF-alpha and oncostatin M. PLoS One 2014; 9: e101937.CrossRefGoogle Scholar
  10. 10.
    Zaba LC, Cardinale I, Gilleaudeau P, et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med 2007; 204: 3183–94.CrossRefGoogle Scholar
  11. 11.
    Zaba LC, Suarez-Farinas M, Fuentes-Duculan J, et al. Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes. J Allergy Clin Immunol 2009; 124: 1022–110.CrossRefGoogle Scholar
  12. 12.
    Wang F, Smith N, Maier L, et al. Etanercept suppresses regenerative hyperplasia in psoriasis by acutely downregulating epidermal expression of IL-19, IL-20 and IL-24. Br J Dermatol 2012; 167: 92–102.CrossRefGoogle Scholar
  13. 13.
    Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol 2008; 58: 106–15.CrossRefGoogle Scholar
  14. 14.
    Saurat JH, Stingl G, Dubertret L, et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol 2008; 158: 558–66.CrossRefGoogle Scholar
  15. 15.
    Thaçi D, Ortonne JP, Chimenti S, et al. A phase IIIb, multicentre, randomized, double-blind, vehicle-controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study. Br J Dermatol 2010; 163: 402–11.CrossRefGoogle Scholar
  16. 16.
    Mrowietz U, Kragballe K, Reich K, et al. An assessment of adalimumab efficacy in three Phase III clinical trials using the European Consensus Programme criteria for psoriasis treatment goals. Br J Dermatol 2013; 168: 374–80.CrossRefGoogle Scholar
  17. 17.
    Soegaard-Madsen L, Johansen C, Iversen L, Kragballe K. Adalimumab therapy rapidly inhibits p38 mitogen-activated protein kinase activity in lesional psoriatic skin preceding clinical improvement. Br J Dermatol 2010; 162: 1216–23.CrossRefGoogle Scholar
  18. 18.
    Johansen C, Vinter H, Soegaard-Madsen L, et al. Preferential inhibition of the mRNA expression of p38 mitogen-activated protein kinase regulated cytokines in psoriatic skin by anti-TNFα therapy. Br J Dermatol 2010; 163: 1194–204.CrossRefGoogle Scholar
  19. 19.
    Johansen C, Funding AT, Otkjaer K, et al. Protein expression of TNF-α in psoriatic skin is regulated at a posttranscriptional level by MAPK-activated protein kinase 2. J Immunol 2006; 176: 1431–8.CrossRefGoogle Scholar
  20. 20.
    Balato A, Schiattarella M, Di Caprio R, et al. Effects of adalimumab therapy in adult subjects with moderate-to-severe psoriasis on Th17 pathway. J Eur Acad Dermatol Venereol 2014; 28: 1016–24.CrossRefGoogle Scholar
  21. 21.
    Johnston A, Guzman AM, Swindell WR, et al. Early tissue responses in psoriasis to the antitumour necrosis factor-alpha biologic etanercept suggest reduced interleukin-17 receptor expression and signalling. Br J Dermatol 2014; 171: 97–107.CrossRefGoogle Scholar
  22. 22.
    Lowes MA, Suarez-Farinas M, Krueger JG. Immunology of psoriasis. Annu Rev Immunol 2014; 32: 227–55.CrossRefGoogle Scholar

Copyright information

© JLE/Springer 2018

Authors and Affiliations

  • Amandine Buffiere-Morgado
    • 1
    • 2
  • Elodie Couderc
    • 1
    • 2
  • Adriana Delwail
    • 3
  • Laure Favot
    • 2
  • Jean-François Jegou
    • 2
  • Elisabeth Solau
    • 1
    • 2
  • Gérard Guillet
    • 1
    • 2
  • Jean-Claude Lecron
    • 1
    • 2
  • Frank Morel
    • 2
    Email author
  1. 1.CHU de PoitiersPoitiersFrance
  2. 2.Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITECUniversité de PoitiersPoitiersFrance
  3. 3.ImageUP, STIM, ERL 7368Université de PoitiersPoitiersFrance

Personalised recommendations