Journal of Allergy and Clinical Immunology最新文献

{"title":"Single-cell RNA sequencing of chronic idiopathic erythroderma defines disease-specific markers.","authors":"Sumanth Chennareddy, Katharina Rindler, Shannon Meledathu, Malini P Naidu, Natalia Alkon, John R Ruggiero, Lisa Szmolyan, Wolfgang Weninger, Wolfgang M Bauer, Johannes Griss, Constanze Jonak, Patrick M Brunner","doi":"10.1016/j.jaci.2024.11.037","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.037","url":null,"abstract":"<p><strong>Background: </strong>Chronic erythroderma is a potentially life-threatening condition that can be caused by a variety of diseases, but approximately 30% of cases remain idiopathic, often with insufficient treatment options.</p><p><strong>Objective: </strong>To establish a molecular disease map of chronic idiopathic erythroderma.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing combined with T-cell receptor sequencing of blood and skin from 5 chronic idiopathic erythroderma (CIE) patients and compared results with 8 cases of erythrodermic cutaneous T-cell lymphoma (eCTCL), 15 moderate-to-severe atopic dermatitis (AD), 10 psoriasis and 20 healthy control (HC) individuals.</p><p><strong>Results: </strong>In erythrodermic CTCL, we found strong expansion of CD4+ malignant clones with a CCR7+SELL+ central memory phenotype. By contrast, CIE exhibited a pattern of low-level, but consistent expansion of CD8A+KLRK1+ T-cell clones, both in blood and skin. KLRK1 was also expressed by CCR10+FUT7+ skin-homing CIE blood T-cells that had increased proliferation rates and were absent in all other conditions. While CIE and CTCL patients lacked the strong type 2 or type 17 immune skewing typically found in AD or psoriasis, respectively, they were characterized by upregulation of MHC II genes (HLA-DRB1, HLA-DRA, CD74) in keratinocytes and fibroblasts, most likely in an IFNG-dependent fashion. However, we found strongest upregulation of type 1 immune mediators in CIE samples, both in the expanded CD8A+ clones, as well as in the tissue microenvironment.</p><p><strong>Conclusion: </strong>Despite the notion that CIE might be a mere bundle of various yet uncharacterized disease processes, we found specific pathogenic signatures in these patients, that were different from other forms of erythroderma. These data might help to improve our pathogenic understanding of the blood and skin compartments of CIE, aiding in discovery of future treatment targets.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854262","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":"Successful hematopoietic cell transplantation utilizing myeloablative reduced-toxicity conditioning in Chediak-Higashi syndrome.","authors":"Alan Bidgoli, Binni Kunvarjee, Andromachi Scaradavou, Richard J O'Reilly, Jaap Jan Boelens, Susan E Prockop, Joseph H Oved","doi":"10.1016/j.jaci.2024.11.014","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.014","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846791","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":"Clinical Response and Corresponding Blood Transcriptome Pathways Pre- And Post-Treatment Of Hereditary Angioedema Prodromes Compared To Active Swelling Attacks.","authors":"Debajyoti Ghosh, John Anderson, Umesh Singh, Cheryl K Bernstein, Jonathan A Bernstein","doi":"10.1016/j.jaci.2024.11.035","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.035","url":null,"abstract":"<p><strong>Rationale: </strong>Approximately 85% Hereditary angioedema (HAE) attacks are associated with prodromal symptoms. We investigated the clinical effect of treating HAE-C1 inhibitor (HAE-C1INH) Type 1 patients with Conestat Alfa® (recombinant human C1-INH) during their prodrome versus an active swelling episode and associated changes in blood transcriptomic genes and pathways pre- vs. post-treatment.</p><p><strong>Methods: </strong>A two-center, unblinded, case-crossover study randomly assigned HAE-C1INH Type 1 patients (N=5) to prodrome or attack-treatment groups; after a patient was treated for either two prodromes or two HAE attacks they were crossed-over to be treated for two HAE attacks or two prodromes. All patients were treated during the prodrome or acute attack with Conestat Alfa® (50 IU/kg body wt., max. 4200 IU for body weight ≥85kg). Blood samples for analysis by RNAseq were obtained at (i) baseline and (ii) during the prodrome before and after treatment and (iii) during an attack before and after treatment. Differentially regulated genes and pathways were elucidated by Ingenuity Pathway Analysis (IPA, Qiagen).</p><p><strong>Results: </strong>Treatment during the HAE prodrome with Conestat Alfa® was as effective at preventing progression to a swelling episode as treatment of an acute attack. HAE prodromes were associated with upregulation of multiple inflammatory extracellular matrix genes, neuropeptide, and inflammasome member genes (e.g., SPARCL1, AGRP, NLRP9; log FC = 4.1, 3.9 and 3.0, respectively). TNF-a and IL-10 were two major hub genes in prodrome-associated enriched gene networks. Conestat Alfa® treatment resulted in reversal of the disease signature in HAE-associated dysregulated pathways. Approximately 42% of prodrome-associated Differentially Expressed Genes (DEGs) were also associated with HAE attacks. The enriched gene networks with hub genes for prodrome (ERK and VEGF) and for acute attack (Insulin and SERPINA1) stages of HAE were identified. The major enriched pathways shared between HAE prodrome and attack were associated with neutrophil function and prostaglandin metabolism.</p><p><strong>Conclusion: </strong>Treatment of HAE-C1INH Type 1 patients who have a well-defined prodrome that historically results in an acute attack may be justified clinically and mechanistically. This approach would represent a paradigm shift for management of HAE on-demand treatment.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828271","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":"CAR-T cell therapy : recent updates and challenges in autoimmune diseases.","authors":"Blandine Caël, Elodie Bôle-Richard, Francine Garnache-Ottou, François Aubin","doi":"10.1016/j.jaci.2024.12.1066","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1066","url":null,"abstract":"<p><p>Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies, demonstrating significant clinical efficacy and leading to FDA approval of several CAR-T cell-based products. This success has prompted exploration of CAR-T cell therapy in other disease areas, including autoimmune diseases (AIDs). CAR-T cells targeting B cells have been shown to provide clinical and biological improvements in patients with refractory AIDs. The aim of this review is to discuss promising strategies involving CAR-T cells in AIDs, such as those targeting B cells and T cells, and to explore new approaches targeting fibroblasts or plasmacytoid dendritic cells. Despite these advances, the application of CAR-T cell therapy in AIDs faces several unique challenges. The quality and functionality of T cells in patients with AIDs may be compromised due to previous treatments and the underlying inflammatory state, affecting the generation and efficacy of CAR-T cells. In addition, achieving adequate tissue biodistribution and persistence of CAR-T cells in affected tissues remains a major challenge. Finally, the high costs associated with CAR-T cell production pose economic problems, particularly in the context of chronic diseases, which are far more numerous than the hematological diseases for which CAR-Ts have been granted marketing authorization to date. If the indications for CAR-T cells increase significantly, production costs will have to drop drastically in order to obtain reliable economic models.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828829","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":"Mortality in adult patients with chronic spontaneous urticaria: A real world cohort study.","authors":"Pavel Kolkhir, Katja Bieber, Tomasz Hawro, Khalaf Kridin, Marlene A Ludwig, Henning Olbrich, Martin Metz, Artem Vorobyev, Ralf J Ludwig, Marcus Maurer","doi":"10.1016/j.jaci.2024.11.036","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.036","url":null,"abstract":"<p><strong>Background: </strong>Chronic spontaneous urticaria (CSU), a common and debilitating disease, is widely held not to be life-limiting, but the mortality of CSU has not been investigated.</p><p><strong>Objective: </strong>To assess all-cause mortality in CSU patients, risk for comorbidities that are leading causes of death and impact of guideline-recommended urticaria treatments on mortality rates.</p><p><strong>Methods: </strong>This is a retrospective population-based cohort study of electronic health records of 272,190 adult CSU patients and 12,728,913 non-urticaria controls from the US Collaborative TriNetx Analytics Network.</p><p><strong>Results: </strong>The study included 264,680 propensity score-matched patients with CSU (mean [SD] age, 47.5 [19.8] years; 71.5% female) and a corresponding number of non-urticaria controls. Patients with CSU had a higher three-month, one-year, and five-year all-cause mortality (hazard ratio, HR=2.09, 95% CI=1.97-2.21, HR=1.77, 95% CI=1.71-1.83, and HR=1.69, 95% CI=1.65-1.73, respectively; all p<0.0001). As compared to non-CSU controls, CSU patients exhibited higher risk and rates of the leading causes of death in the US including suicidal ideations/suicide attempts (HR=3.14, 95% CI=3.00-3.28), and malignant neoplasms (HR=2.09, 95% CI=2.02-2.16). The risk of mortality in CSU appeared to be more pronounced in White and younger patients. All-cause mortality rates at 5 years were significantly lower in CSU patients treated with second generation H1-antihistamines versus untreated patients (1.0% vs. 2.3%, HR=1.84, p<0.0001) and omalizumab-treated patients versus antihistamine-treated patients (0.7% vs. 2.6%, HR=3.99, p=0.003).</p><p><strong>Conclusion: </strong>CSU is associated with increased mortality likely due to comorbidities, especially suicide, and effective CSU treatment may reduce mortality. These findings should be investigated in additional studies, also in other populations.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828364","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":"Splice site and de novo variants can cause PLCG2-associated immune dysregulation with cold urticaria (PLAID-CU).","authors":"Sophia R Chou, Alexis C Bailey, Kathleen Baysac, Andrew J Oler, Joshua D Milner, Michael J Ombrello","doi":"10.1016/j.jaci.2024.06.025","DOIUrl":"10.1016/j.jaci.2024.06.025","url":null,"abstract":"<p><strong>Background: </strong>Phospholipase Cγ2 (PLCγ2) is an important signaling molecule that receives and transmits signals from various cell surface receptors in most hematopoietic lineages. Variants of PLCG2 cause PLCγ2-associated immune dysregulation (PLAID), a family of conditions that are classified by mutational effect. PLAID with cold urticaria (PLAID-CU) is caused by in-frame deletions of PLCG2 that are dominant negative at physiologic temperatures but become spontaneously active at sub-physiologic temperatures.</p><p><strong>Objective: </strong>To identify genetic lesions that cause PLAID by combining RNA sequencing of full-length PLCG2 with whole genome sequencing.</p><p><strong>Methods: </strong>We studied nine probands with antibody deficiency and a positive evaporative cooling test, together with two known PLAID-CU patients and three healthy subjects. Illumina sequencing was performed on full-length PLCG2 cDNA synthesized from peripheral blood mononuclear cell RNA and whole genome sequencing was used to identify genetic lesions. Novel alternate transcripts were overexpressed in the Plcg2-deficient DT40 cell overexpression system. ERK phosphorylation was quantified by flow cytometry with and without BCR crosslinking.</p><p><strong>Results: </strong>Two probands expressed novel alternative transcripts of PLCG2 with in-frame deletions. Proband 1, expressing PLCG2 without exons 18-19, carried a splice site mutation in intron 19. Proband 2, expressing PLCG2 without exons 19-22, carried a 14kb de novo deletion of PLCG2. DT40 cells overexpressing the exon 18-19 or exon 19-22 deletions failed to phosphorylate ERK in response to BCR crosslinking.</p><p><strong>Conclusion: </strong>In addition to autosomal dominant genomic deletions, de novo deletions and splice site mutations of PLCG2 can also cause PLAID-CU. All of these can be identified by cDNA-based sequencing.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817884","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":"Neonatal gut microbiota and risk of developing food sensitization and allergy.","authors":"Ryohei Shibata, Yumiko Nakanishi, Wataru Suda, Taiji Nakano, Noriko Sato, Yosuke Inaba, Yohei Kawasaki, Masahira Hattori, Naoki Shimojo, Hiroshi Ohno","doi":"10.1016/j.jaci.2024.10.029","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.029","url":null,"abstract":"<p><strong>Background: </strong>Food sensitization (FS) develops in early infancy and is a risk factor for subsequent food allergy (FA). Recent evidence suggests relationships of gut microbiota with FS and FA. However, little is known about the role of neonatal gut microbiota in the pathobiology of these manifestations.</p><p><strong>Objectives: </strong>We sought to characterize gut microbiota in children using an enterotyping approach and determine the association of gut microbiota and the enterotypes with the development of FS and FA.</p><p><strong>Methods: </strong>We combined gut microbiome and fecal short-chain fatty acid data from 2 longitudinal birth-cohort studies in Japan, clustered the microbiome data from children who were 1 week to 7 years old and their mothers and identified enterotypes. We also determined the associations of gut microbiota and enterotypes with risks of developing FS and FA across the 2 studies using multivariable regression models.</p><p><strong>Results: </strong>Data from the 2563 microbiomes identified 6 enterotypes. More gut bacteria (eg, Bifidobacterium) in 1-month-old children showed significant relationships with the development of FS and FA than in 1-week-old children. Enterotypes at 1 month old consisted of Bacteroides-dominant, Klebsiella-dominant, and Bifidobacterium-dominant enterotypes. Bifidobacterium-dominant enterotypes with the highest fecal propionate concentration had the lowest risks of developing FS and FA, especially of hen egg white sensitization. Bifidobacterium-dominant enterotypes had lower risks at 2 years old in one study (vs Bacteroides-dominant enterotype, adjusted odds ratio [adjOR]: 0.10, 95% CI: 0.01-0.78; vs Klebsiella-dominant enterotype, adjOR: 0.10, 95% CI: 0.01-0.77) and at 9 months old in the other study (vs Bacteroides-dominant enterotype, adjOR: 0.33, 95% CI: 0.11-0.91).</p><p><strong>Conclusions: </strong>In these birth-cohort studies, gut microbiome clustering identified distinct neonatal enterotypes with differential risks of developing FS and FA.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846785","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":"Clinician views of patient navigators for underserved adults with asthma: A qualitative analysis.","authors":"Andrea J Apter, Tyra Bryant-Stephens, Hami Park, Lenisha Fergus, Kadel LaRose, Philycia Foote, Freya Nezir, Anna U Morgan, Xiaoyan Han, Knashawn H Morales, Heather Klusaritz","doi":"10.1016/j.jaci.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.007","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813236","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":"Parapsoriasis en plaque, deciphered at single-cell resolution.","authors":"Sijia Wang, Raymond J Cho","doi":"10.1016/j.jaci.2024.11.034","DOIUrl":"10.1016/j.jaci.2024.11.034","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791380","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":"A genome-wide meta-analysis reveals shared and population-specific variants for allergic sensitization.","authors":"Emiko Noguchi, Wataru Morii, Haruna Kitazawa, Tomomitsu Hirota, Kyuto Sonehara, Hironori Masuko, Yukinori Okada, Nobuyuki Hizawa","doi":"10.1016/j.jaci.2024.11.033","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.033","url":null,"abstract":"<p><strong>Background: </strong>Allergic diseases are major causes of morbidity in both developed and developing countries and represent a global burden on health care systems. Allergic sensitization is defined as the production of immunoglobulin E (IgE) specific to common environmental allergens, and it is an important indicator in the assessment of allergic diseases.</p><p><strong>Objectives: </strong>This study aimed to clarify the genetic basis of allergic sensitization.</p><p><strong>Methods: </strong>We performed a genome-wide association study (GWAS) of allergic sensitization in the Japanese population, followed by a cross-ancestry meta-analysis with a European population, involving a total of 20,492 cases and 23,342 controls for Japanese and 8,246 cases and 16,786 controls for Europeans. We also performed a polysensitization GWAS of a Japanese population involving 4,923 cases and 17,009 controls.</p><p><strong>Results: </strong>A total of 18 susceptibility loci for Japanese only and 23 allergic sensitization loci for the cross-ancestry population were identified by GWAS, among which 4 loci were novel. We also identified 8 GWAS significant loci for polysensitization. Expression quantitative trait locus colocalization analysis revealed polysensitization GWAS significant variants affecting both the phenotype and expression of the CD28, LPP, and LRCC32 genes. Cross-population genetic correlation analysis of allergic sensitization suggested that heterogeneity exists in allergic sensitization between Europeans and Japanese, indicating that more genetic heterogeneity may exist in allergic sensitization than allergic diseases.</p><p><strong>Conclusions: </strong>Our investigation provided new insights into the molecular mechanism of allergic sensitization that could enhance current understanding of allergy and allergic diseases.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791379","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}