Elevated Type 2 Inflammatory Factors, Th2/Th1 Balanced Status, and Exosomes as a Marker of Severity in Chronic Actinic Dermatitis

Mediators of Inflammation, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Chronic actinic dermatitis (CAD) is a skin inflammation triggered by light exposure, occurring at the exposed site and potentially causing widespread throughout body. While we hypothesize that severe CAD could progress to atopic dermatitis, exact inflammatory mechanisms pathogenesis remain unclear. Objective: We aimed investigate relationships between severity clinical immunological parameters. Methods: patients were classified into two groups based on severity: mild CAD. assessed total IgE levels, eosinophil count in peripheral blood (PB), ratio of Th2 cell percentage Th1 percentages (Th2/Th1), cytokine/chemokine levels both PB lesions. Results: In our study, counts with significantly higher than those control group ( p < 0.05). It was exhibited Th2/Th1 severe‐CAD compared mild‐CAD There significant increases IL‐4, IL‐5, IL‐8, IL‐31, IFN‐ γ lesions Additionally, level CD63 exosomes elevated Persistent elevations associated balance status Conclusion: Severe demonstrates shift toward immunity from Th2/Th1, accompanied factors such as lesions, well increased PB. Thus, consequently, imbalance may contribute systemic manifestations observed patients.

Language: Английский

---

Clinical and Pathophysiological Tangles Between Allergy and Autoimmunity: Deconstructing an Old Dichotomic Paradigm

Clinical Reviews in Allergy & Immunology, Journal Year: 2025, Volume and Issue: 68(1)

Published: Feb. 11, 2025

Allergic and autoimmune disorders are characterised by dysregulation of the immune responses to otherwise inert environmental substances autoantigens, leading inflammation tissue damage. Their incidence has constantly increased in last decades, their co-occurrence defies current standards patient care. For years, allergy autoimmunity have been considered opposite conditions, with IgE Th2 lymphocytes cascade driving canonical allergic manifestations Th1/Th17-related pathways accounting for autoimmunity. Conversely, growing evidence suggests that these conditions not only share some common inciting triggers but also subtended overlapping pathogenic pathways. Permissive genetic backgrounds, along epithelial barrier damage changes microbiome, now appreciated as risk factors both Eosinophils mast cells, autoreactive IgE, emerging players triggering sustaining autoimmunity, while pharmacological modulation B cells Th17 provided novel clues pathophysiology allergy. By combining clinical therapeutic data from mechanistic studies, this review provides a state-of-the-art update on complex interplay between deconstructing old dichotomic paradigms offering potential future research.

Language: Английский

---

IL‐33‐Induced TREM2⁺ Macrophages Promote Pathological New Bone Formation Through CREG1‐IGF2R Axis in Ankylosing Spondylitis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Abstract Pathological new bone formation is the main cause of disability in ankylosing spondylitis (AS), and so far, it lacks a targeted therapy. Macrophages are central orchestrators inflammation progression tissue remodeling, but their contribution to pathological has largely not been explored. Here, identified that TREM2 + macrophages predominated within sites adjacent osteogenic precursor cells. In vivo, both depletion knockout Trem2 significantly reduced collagen antibody‐induced arthritis (CAIA) model. Specifically, promoted differentiation ligament‐derived progenitor cells (LDPCs) by secreting CREG1, secretory glycoprotein involved cell normal physiology. CREG1‐IGF2R‐PI3K‐AKT signaling pathway macrophage‐mediated formation. addition, found IL‐33 macrophage through phosphorylation STAT6. Targeting above signalings alleviated CAIA The findings highlight critical role IL‐33‐induced provide potential therapeutic targets for halting spinal ankylosis AS.

Language: Английский

---

Comparing novel treatments in chronic spontaneous urticaria: A critical appraisal of Bruton's tyrosine kinase inhibitors versus anti‐cytokine biologics in clinical trials

Clinical and Translational Allergy, Journal Year: 2025, Volume and Issue: 15(4)

Published: March 27, 2025

To the Editor, We have been following recent clinical trials focusing on new therapies to treat Chronic Spontaneous Urticaria (CSU). While current treatments can manage debilitating symptoms, a significant number of patients do not achieve symptom control with available medications, including anti-IgE treatment.1, 2 New potential solutions address this include Bruton's tyrosine kinase (BTK) inhibitors, targeting downstream signaling Immunoglobulin E high-affinity receptor,3, 4 and anti-cytokine biologics, T2/alarmin-driven responses.5 However, literature provides limited comparisons between newer CSU treatments. critically appraised efficacy safety six randomized controlled (RCTs), three BTK inhibitors cytokine blockers, provide insights into more promising therapeutic options for CSU. Using Arksey O'Malley's framework, we systematically reviewed relevant trials. Our search across Embase Ovid identified 473 studies from April 2019 May 2024. A secondary ClinicalTrials.gov yielded 123 trials, 15 blockers. Based CONSORT checklist methodological quality,6 selected scoring minimum 10 positive or partially met items out 25. Six RCTs two pharmaceutical releases (for trial NCT05107115, whose results were published at time search) chosen (Figure 1A, Table 1). The outlook Tyrosine Kinase strategies chronic spontaneous urticaria. (A) PRISMA diagram screened records. Eligibility was assessed based 2010 checklist. (B) Demographic non-demographic metrics placebo treated cohorts used assess external validity different studies. Where provided by study authors, weighted average standard deviation calculated ($). (C) Efficacy best treatment arm measured using Activity Score over 7 days (UAS7). Results are presented as net difference in UAS7 scores end (EOS) baseline, normalized subtracting obtained group (ΔUAS7). Percent subjects achieving complete (UAS7 ≤6 EOS) percentage percent observed arm. (D) reported serious adverse events (SAE) placebo. #Average same dose regimen. *Participants received Benralizumab 60 mg Q4W until week 12, then 30 24, followed Q8W 52. BID, twice day; N/A, information available; Q2W, every weeks; SAE, events; TID, times day. Common inclusion criteria included duration least 6 months non-response second-generation H1-antihistamines, while exclusion infections, other dermatological conditions, immunocompromised status, major health conditions. Selected compared areas: characteristics demographic (e.g., participants, age, gender distribution, ethnic diversity, dropout rates); outcome measures days, UAS7); frequency events. Data effect, statistical differences original authors. Studies NCT03137069 NCT04180488 involved similar dosage protocols, respectively fenebrutinib 200 BID dupilumab 300 SC Q2W. Combined p values Fisher's combined probability test, survival function chi-squared distribution computed chi2.sf scipy Python library.7 In multiple dosages, most effective regimen, resulting decrease baseline endpoint (Normalized ΔUAS7 = [(UAS7End – UAS7Baseline)]Treatment UAS7Baseline)]Placebo). Given design registration global registries, considered internal established. contrast, demographic/non-demographic variables representing populations Out studies, 5 sufficient methods assessment 1B, Although preliminary reports accessible,8, 9 methodology rilzabrutinib/NCT05107115 unpublished time, thus limiting our analysis. Across rate highest benralizumab/NCT04612725 (32.9%) lowest dupilumab/NCT04180488 (0%). Participant numbers ranged 134 311, mean age 42.8–46.4 years female majority (68.7%–77.6%). Racial composition varied significantly, non-white participants ranging 17.7% 37.7%. maintained uniform groups, ensuring acceptable validity. biases could arise slight rates, racial cohorts, especially fenebrutinib/NCT03137069 For instance, higher (84.6% Cohort 1, 73.9% 2) BID-treated arms (78.6% 69.6% (73.5% Group A, 75.9% B) versus Q2W (58.6% 68.5% B). Similarly, drop-out rates differed notably (21.4% 1 vs. 8.7% 2). These discrepancies may also contributed reduction respective arms. When evaluating efficacy, four medications produced statistically improvement symptoms. Remibrutinib administered 25 proved effective, equal −12.34 (p < 0.0001), (200 BID), rilzabrutinib (400 TID) (300 Q2W) −7.72 −6.75 1C). Fenebrutinib displayed well-controlled (30.6% ≤6). On average, inhibitor-based offered 19% greater 55% all blockers combined. less severe (0%–4%) than (4.65%–5.36%, Figure 1D). Overall, remibrutinib emerged per each drug category, relatively lower conclusion, analysis phase demonstrated control, although ongoing 3 still warranted. Except dupilumab, none analyzed addressed response subtype (i.e., type I IIb autoimmune CSU) stratified response. Hence, it remains unclear whether underperforming treatments, like anti-TSLP IL-5 receptor antibodies, offer superior outcomes specific patient groups and/or associated comorbidities.10 Anastasia Diamanti Silvia Bulfone-Paus conceptualized study. performed database analyses. Chiara Tontini created figure table. Diamanti, wrote revised manuscript. funded UK Medical Research Council (MR/W025639/1). authors declare no conflicts interest. request

Language: Английский

---

Efficacy and Safety of Ligelizumab in Chronic Spontaneous Urticaria: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Clinical Drug Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Language: Английский

---

A tri-compound formula comprising ginsenoside Rg1, tetrandrine and icariin alleviates atopic dermatitis symptoms in a mouse model

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156737 - 156737

Published: April 1, 2025

Language: Английский

---

Oral treatment with Rosa multiflora fructus extract modulates mast cells in canine atopic dermatitis

Frontiers in Veterinary Science, Journal Year: 2025, Volume and Issue: 12

Published: April 9, 2025

Canine atopic dermatitis is a hereditary, often pruritic, and predominantly T-cell-driven inflammatory skin disease involving an interplay between barrier abnormalities allergen sensitization. However, progress in developing therapeutics for companion animals remains slow, with few drugs advancing to Phase II clinical trials investigate the underlying mechanisms target animals. While Rosa multiflora fruit extract (RMFE) has been strongly implicated improvement of various diseases, its effects on canine (cAD) putative remain unclear. In this study, we aimed evaluate efficacy RMFE treatment cAD explore mechanisms. was administered orally (repeatedly 2 weeks) ovalbumin (OVA)-induced dermatitis-induced beagles. The were assessed through symptom observation scoring using extent severity index. Additionally, histopathological analysis performed (hematoxylin eosin, Masson's trichrome, toluidine blue). Cluster differentiation 4-positive immunostaining also performed, along cytokine level messenger ribonucleic acid analyses T-helper (Th2) immune response markers modeled skin. improved manifestations cAD, leading modulation inflammation cells. It altered Th2 effector levels. Furthermore, reduced allergic responses AD model dogs by reducing mast cell numbers, inhibiting their activation release mediators, immunoglobulin E (IgE) production. Our results suggest that can modulate Th2-dominant helping reduce AD-induced responses.

Language: Английский

---

Efficacy and Safety Study of Dupilumab in Children with Moderate to Severe Atopic Dermatitis

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(04), P. 2805 - 2813

Published: Jan. 1, 2025

Language: Английский

---

Structural and Functional Insights Into IgE Receptor Interactions and Disruptive Inhibition

Immunological Reviews, Journal Year: 2025, Volume and Issue: 331(1)

Published: April 30, 2025

Immunoglobulin E (IgE) plays a critical role in host defense against parasites and venoms but is also best known for its central involvement allergic reactions. Through interactions with high- low-affinity receptors, FcεRI CD23, respectively, IgE sensitizes mast cells basophils, drives antigen presentation, regulates antibody production, overall amplifies type 2 immunity. The unique conformational flexibility of IgE, particularly within Cε2-Cε4 domains the Fc-region, has emerged as key determinant receptor specificity function. Structural studies have revealed that adopts distinct open closed conformations selectively enable or CD23 binding. These insights reshaped our understanding engagement laid foundation therapeutic targeting approaches IgE:receptor to treat allergies. Initial anti-IgE biologics, such omalizumab, were developed neutralize free circulation prevent While clinically successful, this approach limitations, inefficient receptor-bound requirement prolonged frequent injections achieve benefit. Recent advances led development new class molecules termed "disruptive" inhibitors actively disassemble preformed IgE:FcεRI complexes. By exploiting dynamics, creating steric interference, allosteric mechanisms, these molecules, addition their neutralizing capacity, rapid active desensitization effector cells. In review, we highlight how an improved structural mechanistic receptors guided design next-generation molecules. Such multifunctional biologics might offer faster onset, broader activity, potential use acute situations, setting stage era IgE-targeted therapy.

Language: Английский

---

IgE in the Regulation of Adaptive Immune Responses

Immunological Reviews, Journal Year: 2025, Volume and Issue: 331(1)

Published: May 1, 2025

ABSTRACT Immunoglobulin E (IgE) plays a dual role in the immune system, providing protection against pathogens while also mediating pathological hypersensitivity reactions. Its function is mainly studied context of immediate inflammatory responses, where IgE‐sensitized effector cells, such as mast cells and basophils, are triggered by cross‐linking antigen. An often‐overlooked feature IgE biology its strong ability to boost secondary adaptive thus acting physiological adjuvant. The regulation these responses influenced various factors, including primary Ig structure, post‐translational modifications glycosylations, structural properties antigens, interaction with receptors. Interestingly, not only generates antigen‐specific but IgE‐specific autoimmune responses. Natural IgG anti‐IgE autoantibodies circulate at surprisingly high levels, even healthy individuals, contributing serum levels Understanding emerging concepts, beyond singular focus on initial production cell activation, could contribute better understanding immunological functions IgE. In this review, we aim provide an overview current knowledge immunogenicity. Many open questions remain negative positive feedback mechanisms which regulates response, hope inspire future research into underlying IgE‐regulated their potential implications for therapeutic strategies diseases.

Language: Английский

---