Chrysanthi Skevaki MD , Pavel Tafo PhD , Thomas Bahmer MD , Mustafa Abdo PD, MD , Henrik Watz MD , Frauke Pedersen PhD , Christian Herzmann PD, MD , Klaus F. Rabe PhD, MD, FERS , Harald Renz MD , Wolfgang Andreas Nockher PD, PhD
{"title":"Differential expression of eicosanoid pathways after whole blood stimulation in asthma patients","authors":"Chrysanthi Skevaki MD , Pavel Tafo PhD , Thomas Bahmer MD , Mustafa Abdo PD, MD , Henrik Watz MD , Frauke Pedersen PhD , Christian Herzmann PD, MD , Klaus F. Rabe PhD, MD, FERS , Harald Renz MD , Wolfgang Andreas Nockher PD, PhD","doi":"10.1016/j.waojou.2025.101047","DOIUrl":"10.1016/j.waojou.2025.101047","url":null,"abstract":"<div><h3>Objectives</h3><div>Asthma is a heterogeneous disease regarding its pathophysiology, clinical symptoms, and response to treatment. Eicosanoids are important inflammatory mediators, able to either promote or attenuate the underlying chronic airway inflammation. We compared eicosanoid expression patterns in the blood circulation and in stimulated blood leukocytes of asthma patients to identify differences in eicosanoid release which may be related to airway inflammation.</div></div><div><h3>Methods</h3><div>Blood was collected from 198 adult asthmatic patients and 63 healthy controls, participating in the German Center for Lung Research (DZL) ALLIANCE cohort. Eicosanoid release from leukocytes was analyzed using heparinized whole blood after <em>in vitro</em> stimulation with zymosan. Additionally, circulating eicosanoids were measured directly from ethylenediaminetetraacetic acid (EDTA) plasma. Eicosanoids were extracted via solid phase extraction and quantified by high-performance-liquid-chromatography-tandem-mass-spectrometry (HPLC-MS<sup>2</sup>).</div></div><div><h3>Results</h3><div>Eicosanoid levels were low in blood circulation with no significant differences between asthmatics and controls, except for leukotriene E<sub>4</sub> (LTE<sub>4</sub>) which was slightly elevated in asthmatics. After <em>in vitro</em> stimulation we observed an inhibition of prostaglandin and thromboxane biosynthesis only in patients with severe asthma which was related to the regular use of systemic corticosteroids. In contrast, a significant increase was shown for formation of the 5-Lipoxygenase (5-LOX) product LTE<sub>4</sub> in steroid-naïve asthmatics with moderate as well as severe disease severity but not in subjects with systemic steroid treatment. Furthermore 15-Hydorxyeicosatetraenoic acid (15-HETE) production was elevated in asthmatic patients with mild-to-moderate disease activity but dropped down in severe asthmatics.</div></div><div><h3>Conclusions</h3><div>Profiling of eicosanoid production in stimulated whole blood samples showed a specific biosynthesis pattern of asthmatic patients, which is influenced by the use of systemic corticosteroids.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 4","pages":"Article 101047"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aikaterina Alexiou MSc , Sofia Carreras-Kàtcheff MD , Karin Hartmann MD, PhD , Regina Treudler MD, PhD , Paolo Tassinari MSc , Victoria Cardona MD, PhD , Margitta Worm MD, PhD
{"title":"Efficacy of omalizumab in food allergic adults - A retrospective analysis","authors":"Aikaterina Alexiou MSc , Sofia Carreras-Kàtcheff MD , Karin Hartmann MD, PhD , Regina Treudler MD, PhD , Paolo Tassinari MSc , Victoria Cardona MD, PhD , Margitta Worm MD, PhD","doi":"10.1016/j.waojou.2025.101048","DOIUrl":"10.1016/j.waojou.2025.101048","url":null,"abstract":"<div><h3>Background</h3><div>IgE-mediated food allergy poses a significant public health concern, currently with no approved therapies for adults in Europe. Omalizumab (OMA) used as monotherapy or in conjunction with oral immunotherapy (OIT) has been suggested as an efficacious treatment for severe food allergy. The aim of this study was to analyze real-world data from food-allergic patients treated with OMA.</div></div><div><h3>Methods</h3><div>We included food-allergic patients treated with OMA between 2002 and 2022 throughout Europe. Treatment responders (TR) were identified based on the unresponsiveness to related food allergens (determined by food challenge), reduction in the severity of food allergy and absence of anaphylactic reactions.</div></div><div><h3>Results</h3><div>Sixty-two patients (female n = 39/62, 62.9%; mean age 30.6 years) were included into this analysis, most of whom were polysensitized to more than 2 food allergens (n = 40/62, 64.5%); 45/62 patients (72.6%) received OMA in conjunction with OIT, while the remaining patients underwent OMA monotherapy. The eliciting food allergens were tree nuts (n = 27/62, 43.5%), cow's milk (n = 26/62, 41.9%), and vegetables (n = 25/62, 40.3%). In most cases, OMA was initiated with 300 mg q4w (n = 51/62, 82.3%) dosing. Treatment was tolerated exceptionally well.</div><div>Fifty-two (52/62) patients (83.9%) were classified as treatment responders. Six (6/62) patients (9.7%) developed unresponsiveness, 6/62 (9.7%) had a reduction of the severity of food allergy, and 40/62 (64.5%) had no further anaphylactic reactions during treatment. One (1/62) patient (1.6%) undergoing monotherapy was a non-responder, exhibiting repeated anaphylactic reactions to accidental exposures, and 10/62 patients (16.1%) reported anaphylactic reactions during treatment. In most of these cases, cofactors (n = 5/10, 50%) were present.</div></div><div><h3>Conclusion</h3><div>Our real-world evidence data indicate efficacy and tolerability of OMA for the treatment of IgE-mediated food allergy with and without OIT. As the onset of food related reactions upon treatment was frequently linked to the presence of cofactors, these should be identified and considered in patients with food allergy—not only for diagnosis, but also in treatment settings.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 4","pages":"Article 101048"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Dionelly Murillo-Casas MD , Ricardo Zwiener MD , Pedro Giavina-Bianchi MD, PhD , Verónica Pardo-Manrique MD , Rosalaura Villarreal-González MD, PhD , Olga Patricia Monge-Ortega MD , Margarita María Velásquez-Lopera MD, PhD , Diana Lucia Silva-Espinosa MD , Silvana Marcela Castillo-Loaiza MD , Liliana Eugenia Muñoz-García MD , Maria Camila Garzón-Portilla MD , Yury Juliana León-Hernández , Carlos Daniel Serrano-Reyes MD
{"title":"Latin American guidelines for the diagnosis and treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis","authors":"Andrea Dionelly Murillo-Casas MD , Ricardo Zwiener MD , Pedro Giavina-Bianchi MD, PhD , Verónica Pardo-Manrique MD , Rosalaura Villarreal-González MD, PhD , Olga Patricia Monge-Ortega MD , Margarita María Velásquez-Lopera MD, PhD , Diana Lucia Silva-Espinosa MD , Silvana Marcela Castillo-Loaiza MD , Liliana Eugenia Muñoz-García MD , Maria Camila Garzón-Portilla MD , Yury Juliana León-Hernández , Carlos Daniel Serrano-Reyes MD","doi":"10.1016/j.waojou.2025.101046","DOIUrl":"10.1016/j.waojou.2025.101046","url":null,"abstract":"<div><h3>Background</h3><div>Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous reactions induced by delayed drug hypersensitivity, characterized by their complexity and multisystemic nature. Their diagnosis and management are challenging and require a multidisciplinary approach. Identifying the culprit drug is crucial to ensure that the patient has access to safe therapeutic options in the future. To date, there are no specific Latin American guideline or consensus documents on SJS/TEN.</div></div><div><h3>Objective</h3><div>To develop a Latin American guideline on the clinical diagnosis, management, and treatment of SJS/TEN, based on available scientific evidence and the experience of experts from various medical specialties.</div></div><div><h3>Methods</h3><div>This guideline was developed by a group of Latin American allergists and dermatologists involved in the management of SJS/TEN. A search of scientific publications was conducted, and the expert group evaluated the available evidence in the literature, providing grades of recommendation. In cases where there was insufficient evidence, consensus was reached among the experts.</div></div><div><h3>Results</h3><div>The Latin American guidelines on SJS/TEN were developed, addressing relevant practical aspects of clinical diagnosis, and the identification of culprit drugs using the ALDEN (Algorithm of Drug Causality for Epidermal Necrolysis). It also offers recommendations on management, treatment, and prevention of complications, along with a specific algorithm for disease management. This guideline includes a therapeutic strategy, developed and agreed upon by expert specialists involved in the treatment of SJS/TEN.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 4","pages":"Article 101046"},"PeriodicalIF":3.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between dietary zinc intake and asthma in overweight or obese children and adolescents: A cross-sectional analysis of NHANES","authors":"Yingli lin , Dongshui Kang , Qi Chen","doi":"10.1016/j.waojou.2025.101044","DOIUrl":"10.1016/j.waojou.2025.101044","url":null,"abstract":"","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 4","pages":"Article 101044"},"PeriodicalIF":3.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiangqian Qiu MD , Yinhui Zeng MD , Jinyuan Li MD , Qingxiang Zeng PhD, Xi Luo PhD, Wenlong Liu PhD
{"title":"Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis","authors":"Xiangqian Qiu MD , Yinhui Zeng MD , Jinyuan Li MD , Qingxiang Zeng PhD, Xi Luo PhD, Wenlong Liu PhD","doi":"10.1016/j.waojou.2025.101045","DOIUrl":"10.1016/j.waojou.2025.101045","url":null,"abstract":"<div><h3>Background</h3><div>The follicular regulatory T cells (Tfr) and type 2 follicular helper T (Tfh2) play important roles in the pathogenesis of allergic rhinitis (AR). However, its detailed mechanism underlying the regulation of between Tfr and Tfh in AR is unclear. Apolipoprotein AI (Apo-AI), a well-established anti-inflammatory protein, exhibits anti-inflammatory effects on neutrophils, monocytes, macrophages, eosinophils, and type 2 innate lymphoid cells. We sought to investigate the interaction and mechanism between Apo-AI and Tfr/Tfh2 in AR.</div></div><div><h3>Methods</h3><div>The peripheral Tfh2 and Tfr cells were detected and compared by flow cytometry and their correlation with serum Apo-AI protein expression were analyzed. The effect of Apo-AI on Tfh2 and Tfr cells were determined through detection of functional cytokines and key transcription factors by enzyme-linked immunosorbent assay (ELSIA) or polymerase chain reaction (PCR). A Tfr-Tfh2-B cell coculture system was adopted to investigate the role of Apo-AI. Apo-AI knockout AR mice model was established to verify the results of <em>in vitro</em> studies.</div></div><div><h3>Results</h3><div>The serum Apo-AI concentration was positively correlated with the blood frequencies of Tfr cells and negatively correlated with the blood frequencies of Tfh2 cells in AR patients. Apo-AI inhibited IL-4 and IL-21 protein expression by Tfh2 and promoted IL-10 and TGF-beta protein expression by Tfr. In Tfr-Tfh2-B cell coculture system, Apo-AI attenuated the expression of IL-4, IL-21 and activation-induced cytidine deaminase through inducible costimulator (ICOS)/inducible costimulator ligand (ICOSL) pathways. Apo-AI partially restored the suppressive function of AR-derived Tfr cells. Apo-AI knockout AR mice presented with elevated blood Tfh2 frequencies and decreased blood Tfr frequencies, while administration of anti-ICOSL reversed the effect of Apo-AI.</div></div><div><h3>Conclusion</h3><div>Apo-AI alleviates AR through the regulation of the function of Tfh2 and Tfr, which may serve as a potential treatment target for AR.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 4","pages":"Article 101045"},"PeriodicalIF":3.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Obesity in severe asthma: Unveiling challenges and exploring new therapeutic options","authors":"Mona Al-Ahmad MD , Asmaa Ali MD, PhD","doi":"10.1016/j.waojou.2025.101042","DOIUrl":"10.1016/j.waojou.2025.101042","url":null,"abstract":"","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 4","pages":"Article 101042"},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Liu MM , Lin Yang MD, PhD , Qingxiu Xu MD , Qing Jiang PhD , Nan Huang MD , Wenjing Li PhD , Yaqi Yang MD , Dongxia Ma MD , Le Li MM , Yangxue Fu PhD , Hao Chen PhD , Rongfei Zhu MD, PhD
{"title":"Allergen immunotherapy and dupilumab in atopic dermatitis: Clinical efficacy and disparities in immunological indicators","authors":"Jin Liu MM , Lin Yang MD, PhD , Qingxiu Xu MD , Qing Jiang PhD , Nan Huang MD , Wenjing Li PhD , Yaqi Yang MD , Dongxia Ma MD , Le Li MM , Yangxue Fu PhD , Hao Chen PhD , Rongfei Zhu MD, PhD","doi":"10.1016/j.waojou.2025.101043","DOIUrl":"10.1016/j.waojou.2025.101043","url":null,"abstract":"<div><h3>Objective</h3><div>Allergen immunotherapy (AIT) and dupilumab have been confirmed to improve symptoms of atopic dermatitis (AD); however, the precise immune mechanisms underlying their efficacy and whether they can elicit synergistic immune effects remain not fully elucidated. We aimed to investigate the clinical efficacy and immunological changes in AD patients undergoing AIT, dupilumab, and a combination of AIT and dupilumab treatment.</div></div><div><h3>Methods</h3><div>Clinical data, serum samples, and peripheral blood mononuclear cells (PBMC) were collected from house dust mite (HDM)-sensitized AD patients receiving AIT and/or dupilumab at baseline and 6 months. Changes in clinical efficacy, HDM-specific IgE and IgG<sub>4</sub>, serum cytokines, and lymphocyte subgroups were compared among the treatment groups.</div></div><div><h3>Results</h3><div>A total of 77 AD patients were included, with 39 in the AIT group, 19 in the dupilumab group, and 19 in the AIT combined dupilumab group. The SCORAD scores significantly improved in all groups after 6 months. Levels of HDM-specific IgE and total IgE remained stable in the AIT group but decreased in the dupilumab and combination groups. Levels of IgG<sub>4</sub> against major mite components <em>Der p1</em> and <em>Der p23</em> increased in the AIT group and combined treatment group. Serum cytokine levels showed no significant changes, except for a decrease in CCL17 in the dupilumab group. Th1/Th2 and Th17/Th2 ratios increased after dupilumab treatment. There were notable differences in T cell subpopulations when PBMCs were stimulated with HDM extracts after 6-month treatment, tSNE analysis showed the proportion of IL-4<sup>+</sup>IL-13<sup>+</sup>CRTH2<sup>+</sup>T cells increased in the dupilumab group but had no changes in the AIT and combination group.</div></div><div><h3>Conclusions</h3><div>AIT, dupilumab, and their combination improved clinical symptoms and quality of life in AD patients. AIT promoted allergen-specific IgG<sub>4</sub> production, while dupilumab modulated T cell responses and reduced allergen-specific IgE synthesis. The combination of AIT and dupilumab exhibited the immunological parameter changes characteristic of both treatments but did not result in a significantly greater improvement in AD symptoms.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 3","pages":"Article 101043"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ping-An Zhang MD , Jie-Lin Wang MD , Shi-Yan Fu BD , Hua-Lian Luo BD , Run-Dong Qin PhD , Jing Li MD
{"title":"Mediators of the association between allergic diseases and bronchiectasis: A bi-directional univariable and multivariable Mendelian randomization study and mediation analysis","authors":"Ping-An Zhang MD , Jie-Lin Wang MD , Shi-Yan Fu BD , Hua-Lian Luo BD , Run-Dong Qin PhD , Jing Li MD","doi":"10.1016/j.waojou.2025.101038","DOIUrl":"10.1016/j.waojou.2025.101038","url":null,"abstract":"<div><h3>Background</h3><div>Emerging research indicates that bronchiectasis often coexists with a range of allergic illnesses. The pathogenesis of both conditions is highly complex, involving a variety of interconnected factors, such as immune responses, metabolic pathways, and gut microbiota. However, the precise causal relationship between bronchiectasis and allergy-related conditions remains poorly understood.</div></div><div><h3>Materials and methods</h3><div>We obtained published GWAS datasets for 5 allergic disorders (allergic asthma, allergic rhinitis, atopic conjunctivitis, atopic dermatitis, and chronic rhinosinusitis) and bronchiectasis, along with data on 731 immune cells, 91 inflammatory proteins, 1400 plasma metabolites, and 473 gut microbiotas. Using bi-directional two-sample Mendelian Randomization (TSMR), we explored causal relationships between allergic diseases and bronchiectasis and validated these findings in a replication cohort. We also applied Linkage Disequilibrium Score Regression (LDSC) to assess genetic correlations between the conditions. Additionally, the mediating effects of immune cells, inflammatory proteins, metabolites, and gut microbiota on the relationship between allergic disorders and bronchiectasis were assessed through two-step TSMR and multivariate MR analysis.</div></div><div><h3>Results</h3><div>Our study revealed that allergic asthma, allergic rhinitis, atopic conjunctivitis, and atopic dermatitis all increased the risk of developing bronchiectasis, with no causal relationship identified in the reverse direction. Additionally, positive genetic associations were observed between allergic asthma, allergic rhinitis, atopic dermatitis, and bronchiectasis, respectively. We identified a total of forty immune cells, 5 inflammatory proteins, ninety plasma metabolites, and nineteen gut microbiota species as causal factors contributing to bronchiectasis onset. In mediation analysis, we found that the metabolic ratio of Retinol (Vitamin A) to oleoyl-linoleoyl-glycerol (18:1 to 18:2) was a risk factor for allergic asthma developing bronchiectasis, while the level of CD14 on CD33dim HLA-DR + CD11b + cells was a risk factor for allergic rhinitis. Two specific metabolic ratios—the Aspartate to <em>N</em>-acetylglucosamine to <em>N</em>-acetylgalactosamine ratio and the Methionine to phosphate ratio—served as, respectively, risk and protective factors for atopic dermatitis-developing bronchiectasis.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that allergic asthma, allergic rhinitis, atopic conjunctivitis, and atopic dermatitis increase the risk of developing bronchiectasis, with no evidence of a reverse causal relationship. Specifically, 3 metabolic ratios were identified as mediators between allergic diseases and bronchiectasis. Further studies are needed to clarify the underlying mechanisms.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 3","pages":"Article 101038"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shan Liu BSc , Ze-Lang Cai MS , Jingcheng Liu , Si-Yi Que BSc , Wan-Zhen Hu MS , Liang Chen MS , Jia-Jie Chen PhD , Kunmei Ji PhD
{"title":"The novel house dust mite allergen Der p 39 exacerbates atopic dermatitis-like inflammation in mice by inducing skin barrier dysfunction","authors":"Shan Liu BSc , Ze-Lang Cai MS , Jingcheng Liu , Si-Yi Que BSc , Wan-Zhen Hu MS , Liang Chen MS , Jia-Jie Chen PhD , Kunmei Ji PhD","doi":"10.1016/j.waojou.2025.101036","DOIUrl":"10.1016/j.waojou.2025.101036","url":null,"abstract":"<div><h3>Background</h3><div>House dust mite (HDM) allergens can induce or exacerbate allergic inflammation, including atopic dermatitis (AD). Substances that damage the epithelial barrier can trigger or worsen AD. The mechanism by which the novel HDM allergen Der p 39 induces allergic inflammation remains unclear. Our aim was to investigate the effects of Der p 39 on AD-like inflammation and associated mechanisms.</div></div><div><h3>Methods</h3><div>Dinitrochlorobenzene (DNCB) and Der p 39 were utilized to establish AD model mice. Inflammation severity was evaluated with physiological and morphological assays. The effects of Der p 39 on inflammatory cytokine release and skin barrier protein expression were examined in HaCaT cells (human epidermal keratinocytes). Mitogen-activated protein kinase (MAPK) activation was examined by western blots. MAPK inhibitors were employed to assess MAPK involvement in filaggrin expression.</div></div><div><h3>Results</h3><div>Der p 39 worsened allergic inflammation (tissue thickness) in murine ears pretreated with 1% DNCB. Compared to controls, Der p 39-sensitized tissues showed epidermal and dermal thickening with elevated numbers of mast cells and eosinophils in inflammatory lesions. Der p 39 increased transcription and production of pro-inflammatory interleukins (ILs), down-regulated expression of the skin barrier proteins filaggrin and loricrin, and upregulated phosphorylation of ERK, JNK and p38 in HaCaT cells. Inhibition of MAPK signaling rescued filaggrin expression in Der p 39-treated cells.</div></div><div><h3>Conclusions</h3><div>The HDM allergen Der p 39 enhances allergic inflammation and promotes MAPK pathway-mediated epidermal barrier dysfunction, suggesting that Der p 39 may possess pathogenic and clinically relevant immunomodulatory potential.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"18 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}