An S100A8/A9 neutralizing antibody potently ameliorates contact hypersensitivity and atopic dermatitis symptoms.

Journal of Investigative Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Future Directions and Pipeline Therapies for Hidradenitis Suppurativa

Dermatologic Clinics, Journal Year: 2025, Volume and Issue: 43(2), P. 359 - 371

Published: Jan. 21, 2025

Language: Английский

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The Interleukin-1 Family

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Emerging Therapies for Palmoplantar Pustulosis with a Focus on IL-23 Inhibitors

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(10), P. 3273 - 3273

Published: May 8, 2025

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterized by recurrent pustules, erythema, and scaling on the palms soles, leading to significantly reduced quality of life. Although PPP shares some immunopathological features with psoriasis vulgaris, it distinguished unique genetic predispositions, including higher prevalence in East Asian populations, complex immune profile, particularly dysregulation IL-23/Th17 axis IL-36 cytokines. Recent advances treatment have highlighted IL-23 inhibitors, which target p19 subunit suppress Th17 activation Clinical trials show that inhibitors improve severity patient-reported outcomes while maintaining favorable safety profiles. Notably, guselkumab risankizumab recently been approved for Japan Korea. In contrast, IL-17 blockers yielded mixed results. A recent phase 3 trial demonstrated significant efficacy apremilast treating PPP, suggesting may be promising option PPP. Due PPP’s lower compared clinical remain limited. Further large-scale, controlled studies are needed clarify long-term these therapies diverse populations. This review summarizes emerging evidence other treatments detailing their mechanisms action, efficacy, profiles, current challenges, future perspectives optimizing therapy.

Language: Английский

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Treatment of Netherton syndrome with spesolimab

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

Netherton syndrome (NS) is an autosomal recessive disorder characterized by the triad of congenital ichthyosiform erythroderma or ichthyosis linearis circumflexa, hair shaft abnormalities and high serum IgE levels with atopic manifestations. Therapeutic options for NS are limited, often failing to elicit a satisfactory response in patients. Multiomic analyses revealed IL-36 signature be hallmark NS.1 In this report, we present case successfully treated spesolimab, interleukin (IL)-36R inhibitor. A 5-year-old girl prior diagnosis (due compound heterozygous c.80A>G c.710delT mutations SPINK5 gene) was referred treatment. She presented generalized erythema, scaling severe pruritus. had history at birth, alongside signs delayed growth. The patient first child non-consanguineous parents. Physical examination sparse, brittle eyebrows, superficial scaling, facial redness widespread serpiginous polycyclic erythematous plaques double-edged peripheral on her trunk extremities (Figure 1). Trichoscopy showed invagination consistent trichorrhexis invaginate (bamboo hair). Laboratory investigations demonstrated significantly elevated total level exceeding 5000 KU/L (normal range: 0~100 KU/L). White blood count 20.92 × 10E9/L 4.0~12.0 10E9/L). Her treatment included topical emollients, corticosteroids, calcineurin inhibitors oral antihistamines. However, improvement not significant. Treatment dupilumab 300 mg every 4 weeks attempted but discontinued after 8 due ineffectiveness. After obtaining parental consent, spesolimab initiated monthly dose 450 thereafter. Pruritus Numeric Rating Scale (NRS), Area Severity Assessment (NASA) Ichthyosis Index (IASI) were evaluated baseline 4, 12 post-treatment. Remarkable 2) noted NRS pruritus from 9 4; IASI NASA scores decreased 29 45 7.8 16.4, respectively. diagnosed gene, encoding lymphoepithelial Kazal-type-related inhibitor, novel serine protease inhibitor crucial skin barrier formation immunity. There currently no established NS, existing literature primarily consists individual reports. Traditional therapeutic approaches have shown only limited effectiveness addressing condition. Several reports proven efficacy various biotherapies targeting IL-17A, IL-12/IL-23, IL-4Rα, TNF-α IL-1β paediatric patients.2, 3 our exhibited failure dupilumab, IL-4Rα Recent research has underscored potential interleukin-36-driven inflammatory pathway as effective strategy NS.4 studies IL-17/IL-36 upregulated IL-36-driven immune responses evident both blood.1 Increased expression IL-36α IL-36γ cytokines correlates disease severity.4 patients increased risk Staphylococcus aureus infections, which also activates axis, thereby exacerbating inflammation.5 Spesolimab human antagonistic monoclonal IgG1 antibody that blocks IL36α, IL36β Il36γ-induced activation IL36R. patient, treatment, patient's pruritus, erythema remarkable improvement. Thus, emerges promising NS. Currently, registered clinical trial underway, its outcomes eagerly anticipated. views expressed manuscript those author do necessarily reflect official policy position any institution, organization, employer funding source. No conflicts interest relevant article been reported. parents given written informed consent publication their details. original contributions study article; further inquiries can directed corresponding author.

Language: Английский

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A combination therapy with secukinumab and dupilumab in Netherton syndrome: A prospective pilot study

Journal of the American Academy of Dermatology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Inflammatory Mediators Suppress FGFR2 Expression in Human Keratinocytes to Promote Inflammation

Molecular and Cellular Biology, Journal Year: 2024, Volume and Issue: 44(11), P. 489 - 504

Published: Sept. 28, 2024

Fibroblast growth factors (FGFs) are key orchestrators of development, tissue homeostasis and repair. FGF receptor (FGFR) deficiency in mouse keratinocytes causes an inflammatory skin phenotype with similarities to atopic dermatitis, but the human relevance is unclear. Therefore, we generated a CRISPR/Cas9-induced knockout

Language: Английский

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Floxed Il1rl2 Locus with mCherry Reporter Element Reveals Distinct Expression Patterns of the IL-36 Receptor in Barrier Tissues

Cells, Journal Year: 2024, Volume and Issue: 13(9), P. 787 - 787

Published: May 6, 2024

IL-36 cytokines are emerging as beneficial in immunity against pathogens and cancers but can also be detrimental when dysregulated autoimmune autoinflammatory conditions. Interest targeting activity for therapeutic purposes is rapidly growing, yet many unknowns about the functions of these remain. Thus, availability robust research tools essential both fundamental basic science pre-clinical studies to fully access outcomes any manipulation system. For this purpose, a floxed

Language: Английский

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Identification of plasma protein markers of allergic disease risk: a mendelian randomization approach to proteomic analysis

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: May 22, 2024

Abstract Background While numerous allergy-related biomarkers and targeted treatment strategies have been developed employed, there are still signifcant limitations challenges in the early diagnosis for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework. Methods Large-scale cis-MR was employed estimate effects of thousands plasma on five main Additional analyses including MR Steiger analyzing Bayesian colocalisation, were performed test robustness associations; These findings further validated utilizing meta-analytical methods replication analysis. Both proteome- transcriptome-wide association studies approach applied, then, a protein-protein interaction conducted examine interplay between identified targets existing medications. Results Eleven links atopic asthma (AA), dermatitis (AD), rhinitis (AR). Subsequently, these classified into four distinct target groups, focus tier 1 2 due their higher potential become drug targets. analysis extra validation revealed STAT6 TNFRSF6B be Tier IL1RL2 IL6R AA treatment. Two proteins, CRAT TNFRSF6B, ERBB3, IL6R, MMP12, ICAM1, IL1RL2, linked AD, three MANF, STAT6, TNFSF8, AR. Conclusion protein that promising candidates AA, AR, which influence development diseases expose new diagnostic therapeutic

Language: Английский

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Molecular aspects of Interleukin-36 cytokine activation and regulation

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(4), P. 1591 - 1604

Published: June 28, 2024

Interleukin-36 (IL-36) cytokines are structurally similar to other Interleukin-1 superfamily members and essential convey inflammatory responses at epithelial barriers including the skin, lung, gut. Due their potent effects on immune cells, IL-36 cytokine activation is regulated multiple levels, from expression receptor binding. Different isoforms specific as a consequence of particular danger- or pathogen-associated molecular patterns. by exogenous pathogens, fungi, viruses bacteria but also endogenous factors such antimicrobial peptides cytokines. Processing into bioactive forms necessary for host protection can elevate tissue damage. Indeed, exacerbated signalling hyperactivation linked pathogenesis diseases plaque pustular psoriasis, emphasising importance understanding aspects regulating activation. Here, we summarise facets electrochemical properties, regulation extracellular cleavage various proteases pro-inflammatory anti-inflammatory family members. Additionally, this intriguing subfamily displays many characteristics that unique prototypical IL-1 these key distinctions outlined here.

Language: Английский

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