Interleukin-17A blockade with secukinumab results in decreased neutrophil infiltration in psoriasis: minimally-invasive measurement by tape stripping

Christian Loesche, Frank Kolbinger, Marie-Anne Valentin, Philip Jarvis, Melanie Ceci, Grazyna Wieczorek, Edward Khokhlovich, Irina Koroleva, Gerard Bruin, Frank Sinner, Birgit Aigner, Dhavalkumar D Patel

Abstract

Psoriasis is a well characterized interleukin (IL)-17A-driven skin disease with neutrophil infiltration and epidermal hyperkeratosis. Several biomarkers, most prominently β-defensin-2 (BD-2), have been identified using local and systemic invasive measurements as responsive markers of IL-17A-driven skin pathology. We sought to determine whether measurements of epidermal proteins by tape stripping could offer a minimally-invasive method to assess treatment responses. We compared the expression of 170 proteins in the epidermis (tape stripping) and dermis (open flow microperfusion) of 8 psoriatic subjects before and after administration of a single dose of subcutaneous (s.c.) antiIL-17A mAb secukinumab. Proteomic analyses of tape strips revealed a >3-fold decrease in 32 epidermal and inflammatory cell proteins in response to secukinumab. The epidermal proteins with the largest (>10-fold) decreases were: matrix metalloproteinase-8 (MMP-8, 15.68-fold, p<0.05); myeloperoxidase (MPO, 14.72-fold, p<0.005); IL-8 (11.93-fold, p<0.05); MMP-9 (10.81-fold, p<0.005); and IL-1β (10.35-fold, p<0.05). For these proteins, greater-fold protein changes were detected in the epidermis compared to dermis. Immunohistochemical analysis confirmed that neutrophils are the predominant cell type in psoriatic skin lesions that express MPO, MMP-8 and MMP-9, and that secukinumab treatment dramatically decreases neutrophil accumulation. Thus, tape stripping may be used to assess epidermal neutrophils, and protein biomarker responses to anti-IL-17A therapy in psoriasis.

Keywords

biomarker; IL-17; psoriasis; tape-stripping; epidermis

Full Text:

PDF

References

Lowes M A, Bowcock A M, Krueger J G, 2007, Pathogenesis and therapy of psoriasis. Nature, vol.445: 866–873.

Lowes M A, Russell C B, Martin D A, et al. 2013, The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends in Immunology, vol.34(2): 174–181.

Menter A, Sofen H, Smith S, et al. 2011, An open-label, multicenter study of the efficacy and safety of an AM/PM treatment regimen with clobetasol propionate spray 0.05% and calcitriol ointment 3 microg/g in the management of plaque psoriasis. Cutis, vol.88(1): 46–51.

Patel D D, Kuchroo V K, 2015, Th17 cell pathway in human immunity: lessons from genetics and therapeutic interventions. Immunity, vol.43(6): 1040–1051.

Hueber W, Patel D D, Dryja T, et al. 2010, Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Science Translational Medicine, vol.2(52): 52ra72.

Kolbinger F, Loesche C, Valentin MA, et al. 2016, β-defensin-2 is a responsive biomarker of IL-17A-driven skin pathology in psoriasis. Journal of Allergy and Clini-cal Immunology: (Epub ahead of print).

Krueger J G, Ferris L K, Menter A, et al. 2015, An-ti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. Journal of Allergy and Clinical Immunology, vol.136(1): 116–124.e7.

Krueger J G, Fretzin S, Suárez-Fariñas M, et al. 2012, IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. Journal of Allergy and Clinical Immunology, vol.130(1): 145–154.e9.

Russell C B, Rand H, Bigler J, et al. 2014, Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody. Journal of Immunology, vol.192(8): 3828–3836.

Reich K, Papp K A, Matheson R T, et al. 2015, Evidence that a neutrophil-keratinocyte crosstalk is an early target of IL-17A inhibition in psoriasis. Experimental Dermatology, vol.24(7): 529–535.

Dragatin C, Polus F, Bodenlenz M, et al. 2016, Secukinumab distributes into dermal interstitial fluid of psoriasis patients as demonstrated by open flow microperfusion. Experimental Dermatology, vol.25(2): 157–159.

Li J, Mo H Y, Xiong G, et al. 2012, Tumor microenvi-ronment macrophage inhibitory factor directs the accumulation of interleukin-17-producing tumor-infiltrating lymphocytes and predicts favorable survival in nasopharyngeal carcinoma patients. Journal of Biological Chemistry, vol.287: 35484–35495.

Ramesh R, Kozhaya L, McKevitt K, et al. 2014, Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids. Journal of Experimental Medicine, vol.211(1): 89–104.

Maurer M, von Stebut E. 2004, Macrophage inflammatory protein-1. International Journal of Biochemistry and Cell Biology, vol.36(10): 1882–1886.

Menten P, Wuyts A, Van Damme J, 2002, Macrophage inflammatory protein-1. Cytokine and Growth Factor Re-views, vol.13(6): 455–481.

Beisson F, Aoubala M, Marull S, et al. 2001, Use of the tape stripping technique for directly quantifying esterase activities in human stratum corneum. Analytical Biochemistry, vol.290(2): 179–185.

Suzuki Y, Nomura J, Hori J, et al. 1993, Detection and characterization of endogenous protease associated with desquamation of stratum corneum. Archives for Dermatological Research, vol.285(6): 372–377.

Seo N, Tokura Y, Nishijima T, et al. 2000, Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental tumor immunoprophylaxis. Proceedings of the National Academy of Sciences of the United States of America, vol.97(1): 371–376.

Escobar-Chavez J J, Merino-Sanjuán V, López-Cervantes M, et al. 2008, The tape-stripping technique as a method for drug quantification in skin. Journal of Pharmacy & Pharmaceutical Sciences, vol.11(1): 104–130.

Lademann J, Jacobi U, Surber C, et al. 2009, The tape stripping procedure--evaluation of some critical parame-ters. European Journal of Pharmaceutics and Biophar-maceutics, vol.72(2): 317–323.

Amarbayasgalan T, Takahashi H, Dekio I, et al. 2013, Interleukin-8 content in the stratum corneum as an indicator of the severity of inflammation in the lesions of atopic dermatitis. International Archives of Allergy and Immunology, vol.160(1): 63–74.

Clausen M L, Jungersted J M, Andersen P S, et al. 2013, Human beta-defensin-2 as a marker for disease severity and skin barrier properties in atopic dermatitis. British Journal of Dermatology, vol.169(3): 587–593.

Morita E, Takahashi H, Niihara H, et al. 2010, Stratum corneum TARC level is a new indicator of lesional skin inflammation in atopic dermatitis. Allergy, vol.65(9): 1166– 1172.

Sano Y, Masuda K, Tamagawa-Mineoka R, et al. 2013, Thymic stromal lymphopoietin expression is increased in the horny layer of patients with atopic dermatitis. Clinical and Experimental Immunology, vol.171(3): 330–337.

de Jongh C M, Khrenova L, Kezic S, et al. 2008, Poly-morphisms in the interleukin-1 gene influence the stratum corneum interleukin-1 alpha concentration in uninvolved skin of patients with chronic irritant contact dermatitis. Contact Dermatitis, vol.58(5): 263–268.

Egawa G, Doi H, Miyachi Y, et al. 2013, Skin tape strip-ping and cheek swab method for a detection of filaggrin. Journal of Dermatological Science, vol.69(3): 263–265.

Kezic S, Kammeyer A, Calkoen F, et al. 2009, Natural moisturizing factor components in the stratum corneum as biomarkers of filaggrin genotype: evaluation of minimally invasive methods. British Journal of Dermatology, vol.161(5): 1098–1104.

Kezic S, O'Regan G M, Lutter R, et al. 2012, Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. Journal of Allergy and Clinical Immunology, vol.129(4): 1031–1039.e1.

Di Nardo A, Holmes A D, Muto Y, et al. 2016, Improved clinical outcome and biomarkers in adults with papulo-pustular rosacea treated with doxycycline modified-re-lease capsules in a randomized trial. Journal of the American Academy of Dermatology, vol.74(6): 1086– 1092.

Gambichler T, Kobus S, Kobus A, et al. 2011, Expression of antimicrobial peptides and proteins in etanercept-treated psoriasis patients. Regulatory Peptides, vol. 167(2–3): 163–166.

Munro W J, 1898, Note zur l`histopathologie du psoriasis. Annales de Dermatologie et de Syphiligraphie, vol.9: 961–967.

Keijsers R R M C, Joosten I, van Erp P E J, et al. 2014, Cellular sources of IL-17 in psoriasis: a paradigm shift? Experimental Dermatology, vol.23(11): 799–803.

Shirakata Y, Kishimoto J, Tokumaru S, et al. 2007, Epiregulin, a member of the EGF family, is over-expressed in psoriatic epidermis. Journal of Dermatological Science, vol.45(1): 69–72.

Shirakata Y, Komurasaki T, Toyoda H, et al. 2000, Epiregulin, a novel member of the epidermal growth factor family, is an autocrine growth factor in normal human keratinocytes. Journal of Biological Chemistry, vol.275: 5748–5753.

Berasain C, Avila M A, 2014, Amphiregulin. Seminars in Cell and Developmental Biology, vol.28: 31–41.

Chung E, Cook P W, Parkos C A, et al. 2005, Amphiregulin causes functional downregulation of adherens junctions in psoriasis. Journal of Investigative Dermatology, vol.124(6): 1134–1140.


DOI: http://dx.doi.org/10.18063/APM.2016.02.003
(382 Abstract Views, 226 PDF Downloads)

Refbacks

  • There are currently no refbacks.


Copyright (c) 2016 Christian Loesche, Frank Kolbinger, Marie-Anne Valentin, Philip Jarvis, Melanie Ceci, Grazyna Wieczorek, Edward Khokhlovich, Irina Koroleva, Gerard Bruin, Frank Sinner, Birgit Aigner, Dhavalkumar D Patel

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

 

                                          

Advances in Precision Medicine is a peer-reviewed, open-access journal. All journal content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.