Anti-IL-36R antibodies, potentially useful for the treatment of psoriasis: a patent evaluation of WO2013074569

Wolf, Joel; Ferris, Laura K.

doi:10.1517/13543776.2014.881473

Cited by 22 publications

(12 citation statements)

References 11 publications

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“…The available results emphasize the beneficial effects of targeting the IL‐36 pathway on skin inflammation, for example by blocking IL‐36R . Furthermore, an antibody against IL‐36R has been developed for clinical use in patients with psoriasis . To conclude, based on our data, further research is mandatory to reveal the potential of targeting IL‐36–IL‐36R signalling in the therapy of HS.…”

Section: Discussionsupporting

confidence: 58%

Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop

et al. 2018

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Section: Discussionsupporting

confidence: 58%

Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop

et al. 2018

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“…Our data provide a rational basis for the development of therapies specifically targeting these pathways, particularly the IL-36 system in GPP (48, 49). …”

Section: Discussionmentioning

confidence: 89%

IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis

Johnston

Xing

Wolterink

et al. 2017

Journal of Allergy and Clinical Immunology

288

378

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Background Generalized pustular psoriasis (GPP) is a rare, debilitating, and often life-threatening inflammatory disease characterized by episodic infiltration of neutrophils into the skin, pustule development, and systemic inflammation, which can manifest in the presence or absence of chronic plaque psoriasis (PV). Current treatments are unsatisfactory warranting a better understanding of GPP pathogenesis. Objective To understand better the disease mechanism of GPP to allow improved targeted therapies. Methods We performed a gene expression study on formalin-fixed paraffin-embedded GPP (n=28) and PV (n=12) lesional biopsies and healthy control (n=20) skin. Differential gene expression was analyzed using gene ontology and enrichment analysis. Gene expression was validated with qRT-PCR and immunohistochemistry, and a potential disease mechanism investigated using primary human cell culture. Results Compared with healthy skin, GPP lesions yielded 479 and PV 854 differentially expressed genes respectively, with 184 upregulated in both diseases. We detected significant contributions of IL-17A, TNF, IL-1, IL-36 and interferons in both diseases; although GPP lesions furnished higher IL-1 and IL-36 and lower IL-17A and interferon-γ mRNA expression than PV. We detected prominent IL-36 expression by keratinocytes proximal to neutrophilic pustules and show that both neutrophils and neutrophil proteases activate IL-36. Suggesting another mechanism regulating IL-36 activity, the protease inhibitors serpin A1 and A3, which inhibit elastase and cathepsin G respectively, were upregulated in both diseases and inhibited activation of IL-36. Conclusions Our data indicate sustained activation of IL-1 and IL-36 in GPP, inducing neutrophil chemokine expression, infiltration and pustule formation, suggesting that the IL-1/IL-36 inflammatory axis is a potent driver of disease pathology in GPP.

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“…These findings make the IL-36 system a promising drug target in psoriasis. This is supported by the recent development of an anti-IL-36-receptor antibody (WO2013074569) for clinical use in psoriasis (Wolf and Ferris, 2014).…”

Section: Role Of Il-36c In Inflammatory Skin Diseasesmentioning

confidence: 92%

IL-36γ (IL-1F9) Is a Biomarker for Psoriasis Skin Lesions

D’Erme

Wilsmann‐Theis

Wagenpfeil

et al. 2015

Journal of Investigative Dermatology

217

181

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In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not only psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α (TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses, IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, because of its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.

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Anti-IL-36R antibodies, potentially useful for the treatment of psoriasis: a patent evaluation of WO2013074569

Cited by 22 publications

References 11 publications

Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop

Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop

IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis

IL-36γ (IL-1F9) Is a Biomarker for Psoriasis Skin Lesions

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