Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kolbinger, F; Loesche, C; Valentin, MA; Jiang, X; Cheng, Y; Jarvis, P; Peters, T; Calonder, C; Bruin, G; Polus, F; Aigner, B; Lee, DM; Bodenlenz, M; Sinner, F; Pieber, TR; Patel, DD.
β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis.
J Allergy Clin Immunol. 2017; 139(3):923-932
Doi: 10.1016/j.jaci.2016.06.038
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- Co-Autor*innen der Med Uni Graz
- Pieber Thomas
- Sadoghi Birgit
- Sinner Frank Michael
- Weiss Manfred
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- Abstract:
- IL-17A is a key driver of human autoimmune diseases, particularly psoriasis. We sought to determine the role of IL-17A in psoriasis pathogenesis and to identify a robust and measurable biomarker of IL-17A-driven pathology. We studied 8 healthy subjects and 8 patients with psoriasis before and after administration of secukinumab, a fully human anti-IL-17A mAb, and used a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and lesional skin. For validation, we also tested stored sera from 601 patients with a variety of autoimmune diseases. IL-17A was specifically expressed in lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P < .001). Proteomic and gene transcription analyses revealed dysregulated antimicrobial peptides, proinflammatory cytokines, and neutrophil chemoattractants, levels of which returned to normal after treatment with secukinumab. β-Defensin 2 (BD-2) was identified as a biomarker of IL-17A-driven pathology by comparing protein expression in patients with psoriasis versus that in healthy subjects (5746 vs 82 pg/mL in serum, P < .0001; 2747 vs <218 pg/mL in dermis, P < .001), responsiveness to secukinumab therapy, and synergistic induction by IL-17A and TNF-α in epidermal keratinocytes. In a validation set of sera from 601 patients with autoimmune diseases thought to be IL-17A driven, we found that BD-2 levels are most highly increased in patients with psoriatic skin lesions, and in patients with psoriasis, BD-2 levels correlated well with IL-17A levels (r = 0.70, n = 199, P < .001) and Psoriasis Area and Severity Index scores (r = 0.53, n = 281, P < .001). IL-17A is a primary driver of skin pathology in patients with psoriasis, and serum BD-2 is an easily measurable biomarker of IL-17A-driven skin pathology. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Antibodies, Monoclonal - pharmacology
- Antibodies, Monoclonal - therapeutic use
- Antibodies, Monoclonal, Humanized -
- Autoimmune Diseases - blood
- Biomarkers - blood
- Female -
- Humans -
- Interleukin-17 - blood
- Male -
- Psoriasis - blood
- Psoriasis - drug therapy
- Psoriasis - immunology
- Skin - immunology
- Skin - pathology
- beta-Defensins - blood
- Find related publications in this database (Keywords)
- IL-17
- psoriasis
- secukinumab
- beta-defensin 2
- biomarker
- dermal interstitial fluid
- microperfusion
- psoriatic arthritis
- ankylosing spondylitis
- rheumatoid arthritis
- multiple sclerosis
- autoimmunity