Journal of Allergy and Clinical Immunology最新文献

{"title":"Information for Readers","authors":"","doi":"10.1016/S0091-6749(24)00999-0","DOIUrl":"10.1016/S0091-6749(24)00999-0","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Page A42"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"News & Notes-AAAAI","authors":"","doi":"10.1016/S0091-6749(24)01000-5","DOIUrl":"10.1016/S0091-6749(24)01000-5","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages A46-A47"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human DNA-dependent protein kinase catalytic subunit deficiency: A comprehensive review and update","authors":"","doi":"10.1016/j.jaci.2024.06.018","DOIUrl":"10.1016/j.jaci.2024.06.018","url":null,"abstract":"<div><h3>Background</h3><div>DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has an essential role in the non–homologous end-joining pathway that repairs DNA double-strand breaks in V(D)J recombination involved in the expression of T- and B-cell receptors. Whereas homozygous mutations in <em>Prkdc</em> define the Scid mouse, a model that has been widely used in biology, human mutations in <em>PRKDC</em> are extremely rare and the disease spectrum has not been described so far.</div></div><div><h3>Objectives</h3><div>To provide an update on the genetics, clinical spectrum, immunological profile, and therapy of DNA-PKcs deficiency in human.</div></div><div><h3>Methods</h3><div>The clinical, biological, and treatment data from the 6 cases published to date and from 1 new patient were obtained and analyzed. Rubella PCR was performed on available granuloma material.</div></div><div><h3>Results</h3><div>We report on 7 patients; 6 patients displayed the autosomal recessive p.L3062R mutation in <em>PRKDC</em>-encoding DNA-PKcs. Atypical severe combined immunodeficiency with inflammatory lesions, granulomas, and autoimmunity was the predominant clinical manifestation (n = 5 of 7). Rubella viral strain was detected in the granuloma of 1 patient over the 2 tested. T-cell counts, including naive CD4⁺CD45RA⁺ T cells and T-cell function were low at diagnosis for 6 patients. For most patients with available values, naive CD4⁺CD45RA⁺ T cells decreased over time (n = 5 of 6). Hematopoietic stem cell transplantation was performed in 5 patients, of whom 4 are still alive without transplant-related morbidity. Sustained T- and B-cell reconstitution was observed, respectively, for 4 and 3 patients, after a median follow-up of 8 years (range 3-16 years).</div></div><div><h3>Conclusions</h3><div>DNA-PKcs deficiency mainly manifests as an inflammatory disease with granuloma and autoimmune features, along with severe infections.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages 1300-1312"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Home and school pollutant exposure, respiratory outcomes, and influence of historical redlining","authors":"","doi":"10.1016/j.jaci.2024.06.020","DOIUrl":"10.1016/j.jaci.2024.06.020","url":null,"abstract":"<div><h3>Background</h3><div>The discriminatory and racist policy of historical redlining in the United States during the 1930s played a role in perpetuating contemporary environmental health disparities.</div></div><div><h3>Objective</h3><div>Our objectives were to determine associations between home and school pollutant exposure (fine particulate matter [PM_2.5], NO₂) and respiratory outcomes (Composite Asthma Severity Index, lung function) among school-aged children with asthma and examine whether associations differed between children who resided and/or attended school in historically redlined compared to non-redlined neighborhoods.</div></div><div><h3>Methods</h3><div>Children ages 6 to 17 with moderate-to-severe asthma (N = 240) from 9 US cities were included. Combined home and school exposure to PM_2.5 and NO₂ was calculated based on geospatially assessed monthly averaged outdoor pollutant concentrations. Repeated measures of Composite Asthma Severity Index and lung function were collected.</div></div><div><h3>Results</h3><div>Overall, 37.5% of children resided and/or attended schools in historically redlined neighborhoods. Children in historically redlined neighborhoods had greater exposure to NO₂ (median: 15.4 vs 12.1 parts per billion) and closer distance to a highway (median: 0.86 vs 1.23 km), compared to those in non-redlined neighborhoods (<em>P</em> &lt; .01). Overall, PM_2.5 was not associated with asthma severity or lung function. However, among children in redlined neighborhoods, higher PM_2.5 was associated with worse asthma severity (<em>P</em> &lt; .005). No association was observed between pollutants and lung function or asthma severity among children in non-redlined neighborhoods (<em>P</em> &gt; .005).</div></div><div><h3>Conclusions</h3><div>Our findings highlight the significance of historical redlining and current environmental health disparities among school-aged children with asthma, specifically, the environmental injustice of PM_2.5 exposure and its associations with respiratory health.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages 1159-1168"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonspecific lipid-transfer proteins trigger TLR2 and NOD2 signaling and undergo ligand-dependent endocytosis in epithelial cells","authors":"Nicola Cavallari PhD ,&nbsp;Alexander Johnson PhD ,&nbsp;Christoph Nagl BSc ,&nbsp;Saskia Seiser MSc ,&nbsp;Gerald N. Rechberger PhD ,&nbsp;Thomas Züllig PhD ,&nbsp;Thomas A. Kufer PhD ,&nbsp;Adelheid Elbe-Bürger PhD ,&nbsp;Sabine Geiselhart PhD ,&nbsp;Karin Hoffmann-Sommergruber PhD","doi":"10.1016/j.jaci.2024.07.015","DOIUrl":"10.1016/j.jaci.2024.07.015","url":null,"abstract":"<div><h3>Background</h3><div>Allergens can cross the epithelial barrier to enter the body but how this cellular passage affects protein structures and the downstream interactions with the immune system are still open questions.</div></div><div><h3>Objective</h3><div>We sought to show the molecular details and the effects of 3 nonspecific lipid transfer proteins (nsLTPs; Mal d 3 [allergenic nsLTP1 from apple], Cor a 8 [allergenic nsLTP1 from hazelnut], and Pru p 3 [allergenic nsLTP1 from peach]) on epithelial cell uptake and transport.</div></div><div><h3>Methods</h3><div>We used fluorescent imaging, flow cytometry, and proteomic and lipidomic screenings to identify the mechanism involved in nsLTP cellular uptake and signaling on selected epithelial and transgenic cell lines.</div></div><div><h3>Results</h3><div>nsLTPs are transported across the epithelium without affecting cell membrane stability or viability, and allergen uptake was largely impaired by inhibition of clathrin-mediated endocytosis. Analysis of the lipidome associated with nsLTPs showed a wide variety of lipid ligands predicted to bind inside the allergen hydrophobic cavity. Importantly, the internalization of nsLTPs was contingent on these ligands in the protein complex. nsLTPs were found to initiate cellular signaling via Toll-like receptor 2 but not the cluster of differentiation 1 protein receptor, despite neither being essential for nsLTP endocytosis. We also provide evidence that the 3 allergens induced intracellular stress signaling through activation of the NOD2 pathway.</div></div><div><h3>Conclusions</h3><div>Our work consolidates the current model on nsLTP-epithelial cell interplay and adds molecular details about cell transport and signaling. In addition, we have developed a versatile toolbox to extend these investigations to other allergens and cell types.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages 1289-1299"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TH2 cell compensatory effect following benralizumab treatment for eosinophilic gastritis","authors":"Netali Ben-Baruch Morgenstern PhD ,&nbsp;Yrina Rochman PhD ,&nbsp;Julie M. Caldwell PhD ,&nbsp;Margaret H. Collins MD ,&nbsp;Vincent A. Mukkada MD ,&nbsp;Philip E. Putnam MD ,&nbsp;Scott M. Bolton MD ,&nbsp;Kara L. Kliewer PhD ,&nbsp;Marc E. Rothenberg MD, PhD","doi":"10.1016/j.jaci.2024.07.018","DOIUrl":"10.1016/j.jaci.2024.07.018","url":null,"abstract":"<div><h3>Background</h3><div>Eosinophil accumulation is a main feature of eosinophilic gastritis (EoG) and is associated with its histologic diagnosis and pathology. However, a recent clinical trial has demonstrated that EoG endoscopic, noneosinophil histologic, and clinical features remain persistent despite complete eosinophil depletion.</div></div><div><h3>Objective</h3><div>Our aim was to examine gastric T-cell composition and associated cytokine levels of patients with EoG following benralizumab-induced eosinophil depletion versus following administration of placebo.</div></div><div><h3>Methods</h3><div>A cohort of subjects with EoG from a subset of subjects who participated in a recent phase 2 benralizumab trial was treated for 12 weeks with administration of 3 doses of benralizumab (anti–IL–5 receptor α antibody [n = 5]) or placebo (n = 4). Single-cell suspensions obtained by gastric biopsy were stimulated with phorbol 12,13-dibutyrate and ionomycin in the presence of brefeldin A and monensin. Harvested cells were fixed, stained, and analyzed by flow cytometry to examine T-cell populations and associated cytokines.</div></div><div><h3>Results</h3><div>Following benralizumab treatment but not placebo, blood and gastric eosinophil levels decreased 16-fold and 10-fold, respectively. Whereas histologic score and features were significantly decreased, no change was observed in endoscopic score and features. Following complete eosinophil depletion with benralizumab, gastric T_H2 cell levels were 3-fold higher than the levels in the patients with EoG who were given placebo; and the levels of associated type 2 cytokine production of IL-4, IL-5, and IL-13 in the benralizumab-treated patients were, respectively, 4-, 5.5-, and 2.5-fold, higher than those in the placebo-treated patients.</div></div><div><h3>Conclusion</h3><div>We have identified a putative positive feedback loop whereby eosinophil depletion results in a paradoxic increase in levels of T_H2 cells and derived cytokines; this finding suggests an explanation for the limited success of eosinophil depletion as monotherapy in eosinophil-associated gastrointestinal disorders.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages 1325-1332.e2"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomics reveals organized and distinct immune activation in cutaneous granulomatous disorders","authors":"Joseph Daccache BA ,&nbsp;Eunsuh Park ,&nbsp;Muhammad Junejo MD ,&nbsp;Mariam Abdelghaffar BS ,&nbsp;Erica Hwang BS ,&nbsp;Chitrasen Mohanty MS ,&nbsp;Chandra K. Singh PhD ,&nbsp;Guilin Wang PhD ,&nbsp;John O. Wheeler MS ,&nbsp;Bridget E. Shields MD ,&nbsp;Caroline A. Nelson MD ,&nbsp;Yiwei Wang PhD ,&nbsp;William Damsky MD, PhD","doi":"10.1016/j.jaci.2024.07.021","DOIUrl":"10.1016/j.jaci.2024.07.021","url":null,"abstract":"<div><h3>Background</h3><div>Noninfectious (inflammatory) cutaneous granulomatous disorders include cutaneous sarcoidosis (CS), granuloma annulare (GA), necrobiosis lipoidica (NL), and necrobiotic xanthogranuloma (NXG). These disorders share macrophage-predominant inflammation histologically, but the inflammatory architecture and the pattern of extracellular matrix alteration varies. The underlying molecular explanations for these differences remain unclear.</div></div><div><h3>Objective</h3><div>We sought to understand spatial gene expression characteristics in these disorders.</div></div><div><h3>Methods</h3><div>We performed spatial transcriptomics in cases of CS, GA, NL, and NXG to compare patterns of immune activation and other molecular features in a spatially resolved fashion.</div></div><div><h3>Results</h3><div>CS is characterized by a polarized, spatially organized type 1-predominant response with classical macrophage activation. GA is characterized by a mixed but spatially organized pattern of type 1 and type 2 polarization with both classical and alternative macrophage activation. NL showed concomitant activation of type 1, type 2, and type 3 immunity with a mixed pattern of macrophage activation. Activation of type 1 immunity was shared among, CS, GA, and NL and included upregulation of IL-32. NXG showed upregulation of CXCR4-CXCL12/14 chemokine signaling and exaggerated alternative macrophage polarization. Histologic alteration of extracellular matrix correlated with hypoxia and glycolysis programs and type 2 immune activation.</div></div><div><h3>Conclusions</h3><div>Inflammatory cutaneous granulomatous disorders show distinct and spatially organized immune activation that correlate with hallmark histologic changes.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages 1216-1231"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy","authors":"Witchaya Srisuwatchari MD ,&nbsp;Mayte Suárez-Fariñas PhD ,&nbsp;Andrew D. Delgado PhD ,&nbsp;Galina Grishina MS ,&nbsp;Maria Suprun PhD ,&nbsp;Ashley Sang Eun Lee MD ,&nbsp;Pakit Vichyanond MD ,&nbsp;Punchama Pacharn MD ,&nbsp;Hugh A. Sampson MD","doi":"10.1016/j.jaci.2024.08.003","DOIUrl":"10.1016/j.jaci.2024.08.003","url":null,"abstract":"<div><h3>Background</h3><div>The bead-based epitope assay has been used to identify epitope-specific (es) antibodies and successfully used to diagnose clinical allergy to milk, egg, and peanut.</div></div><div><h3>Objective</h3><div>We sought to identify es-IgE, es-IgG4, and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the bead-based epitope assay.</div></div><div><h3>Methods</h3><div>Children and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled. Seventy-nine peptides from α-/β-gliadin, γ-gliadin, ω-5-gliadin, and high- and low-molecular-weight glutenin were commercially synthesized and coupled to LumAvidin beads (Luminex Corporation, Austin, Tex). Machine learning methods were used to identify diagnostic epitopes, and performance was evaluated using the DeLong test.</div></div><div><h3>Results</h3><div>The analysis included 122 children (83 wheat-allergic and 39 wheat-tolerant; 57.4% male). Machine learning coupled with simulations identified wheat es-IgE, but not es-IgG4 or es-IgG1, to be the most informative for diagnosing wheat allergy. Higher es-IgE binding intensity correlated with the severity of allergy phenotypes, with wheat anaphylaxis exhibiting the highest es-IgE binding intensity. In contrast, wheat-dependent exercise-induced anaphylaxis showed lower es-IgG1 binding intensity than did all the other groups. A set of 4 informative epitopes from ω-5-gliadin and γ-gliadin were the best predictors of wheat allergy, with an area under the curve of 0.908 (sensitivity, 83.4%; specificity, 88.4%), higher than the performance exhibited by wheat-specific IgE (area under the curve = 0.646; <em>P</em> &lt; .001). The predictive ability of our model was confirmed in an external cohort of 71 patients (29 allergic, 42 nonallergic), with an area under the curve of 0.908 (sensitivity, 75.9%; specificity, 90.5%).</div></div><div><h3>Conclusions</h3><div>The wheat bead-based epitope assay demonstrated greater diagnostic accuracy compared with existing specific IgE tests for wheat allergy.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages 1249-1259"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The processed milk hypothesis: A major factor in the development of eosinophilic esophagitis (EoE)?","authors":"James R. Baker Jr. MD ,&nbsp;Roopesh Singh Gangwar PhD ,&nbsp;Thomas A. Platts-Mills MD, PhD","doi":"10.1016/j.jaci.2024.08.015","DOIUrl":"10.1016/j.jaci.2024.08.015","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages 1123-1126"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mepolizumab for episodic angioedema with eosinophilia","authors":"Matthew A. Rank MD","doi":"10.1016/j.jaci.2024.07.028","DOIUrl":"10.1016/j.jaci.2024.07.028","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 5","pages":"Pages 1340-1341"},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}