Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis

Sofen, Howard; Smith, Stacy; Matheson, Robert; Leonardi, Craig L.; Calderón, César; Brodmerkel, Carrie; Li, Katherine; Campbell, Kim; Marciniak, Stanley J.; Wasfi, Y.; Wang, Yuhua; Szapary, Philippe; Krueger, James G.

doi:10.1016/j.jaci.2014.01.025

Cited by 281 publications

(257 citation statements)

References 27 publications

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“…We identified 4 independent gene expression datasets from clinical trials in psoriasis using anti-TNF (etanercept; 2 independent datasets), anti-IL-23 (guselkumab), or anti-IL-17R (brodalumab) (48)(49)(50)(51). Consistent with the gene expression results in Figure 3, in these clinical trials, GRHL3 was significantly upregulated in lesional versus nonlesional skin, and after treatment, this high level was significantly reduced to levels similar to the nonlesional controls in all but 1 etanercept trial, which still showed the correct trend (Supplemental Figure 6, A-D).…”

Section: Grhl3 Is Dispensable For Homeostatic Adult Epidermal Barriermentioning

confidence: 99%

A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia

Gordon¹,

Zeller²,

Klein³

et al. 2014

J. Clin. Invest.

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Section: Grhl3 Is Dispensable For Homeostatic Adult Epidermal Barriermentioning

confidence: 99%

A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia

Gordon¹,

Zeller²,

Klein³

et al. 2014

J. Clin. Invest.

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“…At present, however, biologic therapies directed against only a limited number of cytokines have proven clinically effective, including TNF, IL-17A, and IL-23 [60][61][62]. Of these, IL-17A may represent the most pivotal "hub" within the cytokine network coordinating plaque development, since TNF and IL-23 appear to positively (See figure on previous page.)…”

Section: Discussionmentioning

confidence: 99%

645 Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis

Michaels

Sutter

Diaconu

et al. 2017

Journal of Investigative Dermatology

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“…It became evident that the ustekinumab clinical eicacy was related to inhibition of the IL-23 biological efect. CTLA4-Ig T cell costimulation blockade CD80, CD86 Blocking T cell activation improve psoriasis [11] LFA-3-Ig Memory T cell depletion CD2 Memory T cells are relevant in psoriasis [10] Anti-LFA-1 T cell migration and T-cell costimulation inhibitor LFA-1 Migration of T cells to psoriasis lesion is involved in disease [12] Anti-TNF-α Neutralization of biological selectively IL-23, which also has conirmed the clinical relevance of speciically blocking the IL-23/Th17 in psoriasis [16].…”

Section: Translational Research and Clinically Relevant Pathological mentioning

confidence: 92%

Human Translational Research in Psoriasis Using CLA+ T Cells

Ruiz-Romeu¹,

Santamaria‐Babí²

2017

An Interdisciplinary Approach to Psoriasis

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Focusing on the study of human memory CLA+ T cells to understand psoriasis pathology constitutes an innovative approach to explore the pathological mechanism of this chronic cutaneous inlammatory disease. CLA+ T cells can be considered peripheral cell biomarkers in the study of T-cell mediated human skin diseases. During the last few years, new evidences have been found that link streptococcal infection with IL-17 response in psoriasis by studying the interaction between Streptococcus pyogenes with CLA+ T cells and autologous epidermal cells. S. pyogenes constitutes the best clinically characterized trigger of psoriasis and by exploring its efect on CLA+ T cells and epidermal cells in psoriasis may allow understanding psoriasis by using patient's clinical samples ex vivo. Keywords: psoriasis, CLA+ T cells, translational research, Streptococcus pyogenes, IL17 CLA+ T cells and the regional cutaneous immune systemThe adaptive immune responses taking place during cutaneous chronic inlammation in psoriasis preferentially involve a subset of memory T lymphocytes, which are related to the skin and that belong to the cutaneous immune system, and constitute one of the best characterized regional immune systems of the body and known for decades [1]. In the humans, the cutaneous lymphocyte-associated antigen (CLA) is a surface cell marker that allows identifying T cells that belong to the cutaneous immune system. The CLA antigen is a carbohydrate expressed by 15% of human circulating T cells, and on most (>90%) skin-iniltrating T cells, contrary to other inlamed organs [2]. CLA is expressed preferentially on memory antigenexperienced T cells.© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The CLA is one of the adhesion molecule that, together with chemokine receptors, allows T cells to selectively migrate to the skin, in either homeostatic or inlammatory conditions, by binding to endothelial cell wall via adhesion molecules or ligands. The molecular interactions between CLA/E-selectin, very late antigen-4 (VLA-4)/vascular cell adhesion protein-1 (VCAM-1), lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1), and chemokine ligands for chemokine, C-C motif receptor (CCR) 10, CCR4, CCR6, and CCR8 constitute a code bar system enabling skin iniltration [3].The importance of circulating CLA+ T cells for understanding the skin immune system is not only based on their capacity to selectively migrate to skin, but also on the fact that these circulating memory T cells are functionally related to the immune response taking place in the cutaneous inlamed lesions. This feature is based on the recirculating capacity of those cells between lesional skin and blood during cutaneous inlammation in psoriasis [3]. The adhesive interaction between LFA-1 ...

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Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis

Abstract: IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis.

Cited by 281 publications

References 27 publications

A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia

A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia

645 Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis

Human Translational Research in Psoriasis Using CLA+ T Cells

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