Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis

Nicole Sander; Dora Stölzl; Melina Fonfara; Jan Hartmann; Inken Harder; Ina Suhrkamp; Ivone Jakaša; Ellen van den Bogaard; Ivonne van Vlijmen-Willems; Silke Szymczak; Elke Rodriguez; Sascha Gerdes; Stephan Weidinger

doi:10.1093/bjd/ljae138

Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis

Nicole Sander, Dora Stölzl, Melina Fonfara, Jan Hartmann, Inken Harder, Ina Suhrkamp, Ivone Jakaša, Ellen van den Bogaard, Ivonne van Vlijmen-Willems, Silke Szymczak, Elke Rodriguez, Sascha Gerdes, Stephan Weidinger

Institut für Medizinische Biometrie und Statistik

25 Zitate (Scopus)

Abstract

BACKGROUND: Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab, a monoclonal antibody neutralizing IL-13, reduces inflammation and clinical disease activity, less is known about its effects on barrier function.

OBJECTIVES: To characterize effects of tralokinumab treatment on skin barrier function.

METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor (NMF) content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, non-lesional, and sodium lauryl sulfate (SLS)-irritated skin of 16 AD patients over the course of 16 weeks of tralokinumab treatment.

RESULTS: All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 32.66% (p = 0.01), and SCH increased by 58.44% (p = 0.004), along with histological reduction in spongiosis (p = 0.003), keratin 16 expression and epidermal thickness (p = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and pro-inflammatory proteins such as fibronectin (p = 0.006), CCL17/TARC (p = 0.025) and IL-8 (p = 0.014), with significant changes already at week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2.

CONCLUSION: Tralokinumab treatment improves skin physiology, epidermal pathology, and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis.

Originalsprache	Englisch
Zeitschrift	British Journal of Dermatology
Jahrgang	191
Ausgabenummer	3
Seiten (von - bis)	344-350
Seitenumfang	7
ISSN	0007-0963
DOIs	https://doi.org/10.1093/bjd/ljae138
Publikationsstatus	Veröffentlicht - 09.2024

Fördermittel

This investigator-initiated study was supported by a grant from LEO Pharma. LEO Pharma also provided the investigator medical product. LEO Pharma was not involved in planning, recruiting or conducting the study, or in the process of manuscript writing. This work was also supported by the BIOMAP project. This project received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement 821511. The JU receives support from the European Union's Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). This publication reflects only the authors' views and the JU is not responsible for any use that may be made of the information it contains. This investigator-initiated study was supported by a grant from LEO Pharma. LEO Pharma also provided the investigator medical product. LEO Pharma was not involved in planning, recruiting or conducting the study, or in the process of manuscript writing. This work was also supported by the BIOMAP project. This project received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement 821511. The JU receives support from the European Union\u2019s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). This publication reflects only the authors\u2019 views and the JU is not responsible for any use that may be made of the information it contains. Conflicts of interest S.W. is has received institutional research grants from LEO Pharma, Pfizer and Sanofi; and has performed consultancies and/or lectures for AbbVie, Almirall, Boehringer, Galderma, GSK, LEO Pharma, Lilly, Pfizer, Regeneron and Sanofi. S.G. has been an advisor and/or has received speakers\u2019 honoraria and/or has received grants and/or has participated in clinical trials for the following companies: AbbVie, ACELYRIN, Affibody, Akari Therapeutics, Almirall-Hermal, Amgen, Argenx, Aristea Therapeutics, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Hexal, Incyte, Janssen-Cilag, Klinge Pharma, Kymab, LEO Pharma, Medac, MSD, Neubourg Skin Care, Novartis, Pfizer, Pierre Fabre, Principia Biopharma, Regeneron Pharmaceutical, Sandoz Biopharmaceuticals, Sanofi-Aventis, Trevi Therapeutics and UCB Pharma. E.v.d.B. has received funds from the LEO Foundation and Fagron, has performed consultancies and contract research for NIZO Food Research, and has received in kind contributions for research projects from CELLnTEC and TropIQ Health Services. The other authors declare no conflicts of interest.

Träger	Trägernummer
European Federation of Pharmaceutical Industries and Associations
Horizon 2020 Framework Programme
Innovative Medicines Initiative	821511
LEO Pharma
TropIQ Health Services

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)
Zentren: Center for Research on Inflammation of the Skin (CRIS)

DFG-Fachsystematik

2.22-01 Epidemiologie, Medizinische Biometrie/Statistik
2.22-19 Dermatologie
2.21-05 Immunologie

Dokumente

10.1093/bjd/ljae138

Weitere Links

SFB 1526, PANTAU: Pathomechanismen Antikörpervermittelter Autoimmunerkrankungen
Sadik, C. (Sprecher*in), Zillikens, D. (Sprecher*in), Scheffold, A. (Projektleiter*in (PI)), Schmidt, E. (Projektleiter*in (PI)), Heine, G. (Projektleiter*in (PI)), Manz, R. (Projektleiter*in (PI)), Köhl, J. (Projektleiter*in (PI)), Ludwig, R. (Projektleiter*in (PI)), Peipp, M. (Projektleiter*in (PI)), Hammers, M. C. (Projektleiter*in (PI)), Verschoor, A. (Projektleiter*in (PI)), Karsten, C. (Projektleiter*in (PI)), Nimmerjahn, F. (Projektleiter*in (PI)), Hutloff, A. (Projektleiter*in (PI)), Ibrahim, S. (Projektleiter*in (PI)), Wettschureck, N. (Projektleiter*in (PI)), Bieber, K. (Projektleiter*in (PI)), Schilf, P. (Projektleiter*in (PI)), Vaeth, M. (Projektleiter*in (PI)), Hirose, M. (Projektleiter*in (PI)), Vaeth, M. (Projektleiter*in (PI)), Baines, J. F. (Projektleiter*in (PI)), Bacher, P. (Projektleiter*in (PI)), Hoffmann, M. (Projektleiter*in (PI)), Busch, H. S. (Projektleiter*in (PI)), Höppner, M. (Projektleiter*in (PI)), Becker, M. (Projektleiter*in (PI)), Holtsche, M. M. (Projektleiter*in (PI)), Fähnrich, A. (Projektleiter*in (PI)), Szymczak, S. (Projektleiter*in (PI)), Murthy, S. (Projektleiter*in (PI)) & Lux, A. (Projektleiter*in (PI))
01.01.22 → …
Projekt: DFG Verbundprojekte › DFG Sonderforschungsbereiche / Transregios (SFB/TR)

Zitieren

Sander, N., Stölzl, D., Fonfara, M., Hartmann, J., Harder, I., Suhrkamp, I., Jakaša, I., van den Bogaard, E., van Vlijmen-Willems, I., Szymczak, S., Rodriguez, E., Gerdes, S., & Weidinger, S. (2024). Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis. British Journal of Dermatology, 191(3), 344-350. https://doi.org/10.1093/bjd/ljae138

@article{e01fe5cefa4149c3a5e44f973b01eb68,

title = "Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis",

abstract = "BACKGROUND: Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab, a monoclonal antibody neutralizing IL-13, reduces inflammation and clinical disease activity, less is known about its effects on barrier function.OBJECTIVES: To characterize effects of tralokinumab treatment on skin barrier function.METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor (NMF) content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, non-lesional, and sodium lauryl sulfate (SLS)-irritated skin of 16 AD patients over the course of 16 weeks of tralokinumab treatment.RESULTS: All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 32.66\% (p = 0.01), and SCH increased by 58.44\% (p = 0.004), along with histological reduction in spongiosis (p = 0.003), keratin 16 expression and epidermal thickness (p = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and pro-inflammatory proteins such as fibronectin (p = 0.006), CCL17/TARC (p = 0.025) and IL-8 (p = 0.014), with significant changes already at week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2.CONCLUSION: Tralokinumab treatment improves skin physiology, epidermal pathology, and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis.",

author = "Nicole Sander and Dora St{\"o}lzl and Melina Fonfara and Jan Hartmann and Inken Harder and Ina Suhrkamp and Ivone Jaka{\v s}a and \{van den Bogaard\}, Ellen and \{van Vlijmen-Willems\}, Ivonne and Silke Szymczak and Elke Rodriguez and Sascha Gerdes and Stephan Weidinger",

note = "{\textcopyright} The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].",

year = "2024",

month = sep,

doi = "10.1093/bjd/ljae138",

language = "English",

volume = "191",

pages = "344--350",

journal = "British Journal of Dermatology",

issn = "0007-0963",

publisher = "Oxford University Press",

number = "3",

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Sander, N, Stölzl, D, Fonfara, M, Hartmann, J, Harder, I, Suhrkamp, I, Jakaša, I, van den Bogaard, E, van Vlijmen-Willems, I, Szymczak, S, Rodriguez, E, Gerdes, S & Weidinger, S 2024, 'Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis', British Journal of Dermatology, Jg. 191, Nr. 3, S. 344-350. https://doi.org/10.1093/bjd/ljae138

Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis. / Sander, Nicole; Stölzl, Dora; Fonfara, Melina et al.
in: British Journal of Dermatology, Jahrgang 191, Nr. 3, 09.2024, S. 344-350.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis

AU - Sander, Nicole

AU - Stölzl, Dora

AU - Fonfara, Melina

AU - Hartmann, Jan

AU - Harder, Inken

AU - Suhrkamp, Ina

AU - Jakaša, Ivone

AU - van den Bogaard, Ellen

AU - van Vlijmen-Willems, Ivonne

AU - Szymczak, Silke

AU - Rodriguez, Elke

AU - Gerdes, Sascha

AU - Weidinger, Stephan

N1 - © The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

PY - 2024/9

Y1 - 2024/9

N2 - BACKGROUND: Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab, a monoclonal antibody neutralizing IL-13, reduces inflammation and clinical disease activity, less is known about its effects on barrier function.OBJECTIVES: To characterize effects of tralokinumab treatment on skin barrier function.METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor (NMF) content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, non-lesional, and sodium lauryl sulfate (SLS)-irritated skin of 16 AD patients over the course of 16 weeks of tralokinumab treatment.RESULTS: All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 32.66% (p = 0.01), and SCH increased by 58.44% (p = 0.004), along with histological reduction in spongiosis (p = 0.003), keratin 16 expression and epidermal thickness (p = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and pro-inflammatory proteins such as fibronectin (p = 0.006), CCL17/TARC (p = 0.025) and IL-8 (p = 0.014), with significant changes already at week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2.CONCLUSION: Tralokinumab treatment improves skin physiology, epidermal pathology, and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis.

AB - BACKGROUND: Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab, a monoclonal antibody neutralizing IL-13, reduces inflammation and clinical disease activity, less is known about its effects on barrier function.OBJECTIVES: To characterize effects of tralokinumab treatment on skin barrier function.METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor (NMF) content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, non-lesional, and sodium lauryl sulfate (SLS)-irritated skin of 16 AD patients over the course of 16 weeks of tralokinumab treatment.RESULTS: All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 32.66% (p = 0.01), and SCH increased by 58.44% (p = 0.004), along with histological reduction in spongiosis (p = 0.003), keratin 16 expression and epidermal thickness (p = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and pro-inflammatory proteins such as fibronectin (p = 0.006), CCL17/TARC (p = 0.025) and IL-8 (p = 0.014), with significant changes already at week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2.CONCLUSION: Tralokinumab treatment improves skin physiology, epidermal pathology, and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis.

UR - https://www.mendeley.com/catalogue/52aaa828-f6c5-3b2a-b9b9-3c17d01dcac6/

UR - https://www.scopus.com/pages/publications/85197425157

U2 - 10.1093/bjd/ljae138

DO - 10.1093/bjd/ljae138

M3 - Journal articles

C2 - 38531691

SN - 0007-0963

VL - 191

SP - 344

EP - 350

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 3

ER -

Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis

Abstract

Fördermittel

UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

Dokumente

Weitere Links

Fingerprint

Projekte

SFB 1526, PANTAU: Pathomechanismen Antikörpervermittelter Autoimmunerkrankungen

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