Pub Date : 2024-08-16DOI: 10.1016/j.jaci.2024.08.003
Witchaya Srisuwatchari, Mayte Suárez-Fariñas, Andrew D Delgado, Galina Grishina, Maria Suprun, Ashley Sang Eun Lee, Pakit Vichyanond, Punchama Pacharn, Hugh A Sampson
Background: The bead-based epitope assay (BBEA) has been used to identify epitope-specific (es) antibodies and successfully utilized to diagnose clinical allergy to milk, egg and peanut.
Objective: This study aimed 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 BBEA.
Methods: Children and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled. Seventy-nine peptides from alpha/beta-gliadin, gamma-gliadin (γ-gliadin), omega-5-gliadin (ω-5-gliadin), high and low molecular weight glutenin were commercially synthesized and coupled to LumAvidin beads. Machine learning (ML) methods were used to identify diagnostic epitopes and performance was evaluated using DeLong's test.
Results: The analysis includes 122 children (83 wheat-allergic and 39 wheat-tolerant, 57.4% male). ML coupled with simulations identified wheat es-IgE, but not es-IgG4 or es-IgG1 to be 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 (WDEIA) showed lower es-IgG1 binding than all other groups. A set of 4 informative epitopes from ω-5-gliadin, and γ-gliadin were the best predictors of wheat allergy with an AUC of 0.908 (sensitivity=83.4%, specificity=88.4%), higher than the performance exhibited by wheat-specific IgE (AUC=0.646, p < 0.001). The predictive ability of our model was confirmed in an external cohort of 71 patients (29 allergic, 42 non-allergic), with an AUC of 0.908 (sensitivity=75.9%, specificity=90.5%).
Conclusion: The wheat BBEA demonstrated greater diagnostic accuracy compared to existing specific IgE tests for wheat allergy.
{"title":"Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy.","authors":"Witchaya Srisuwatchari, Mayte Suárez-Fariñas, Andrew D Delgado, Galina Grishina, Maria Suprun, Ashley Sang Eun Lee, Pakit Vichyanond, Punchama Pacharn, Hugh A Sampson","doi":"10.1016/j.jaci.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.08.003","url":null,"abstract":"<p><strong>Background: </strong>The bead-based epitope assay (BBEA) has been used to identify epitope-specific (es) antibodies and successfully utilized to diagnose clinical allergy to milk, egg and peanut.</p><p><strong>Objective: </strong>This study aimed 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 BBEA.</p><p><strong>Methods: </strong>Children and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled. Seventy-nine peptides from alpha/beta-gliadin, gamma-gliadin (γ-gliadin), omega-5-gliadin (ω-5-gliadin), high and low molecular weight glutenin were commercially synthesized and coupled to LumAvidin beads. Machine learning (ML) methods were used to identify diagnostic epitopes and performance was evaluated using DeLong's test.</p><p><strong>Results: </strong>The analysis includes 122 children (83 wheat-allergic and 39 wheat-tolerant, 57.4% male). ML coupled with simulations identified wheat es-IgE, but not es-IgG4 or es-IgG1 to be 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 (WDEIA) showed lower es-IgG1 binding than all other groups. A set of 4 informative epitopes from ω-5-gliadin, and γ-gliadin were the best predictors of wheat allergy with an AUC of 0.908 (sensitivity=83.4%, specificity=88.4%), higher than the performance exhibited by wheat-specific IgE (AUC=0.646, p < 0.001). The predictive ability of our model was confirmed in an external cohort of 71 patients (29 allergic, 42 non-allergic), with an AUC of 0.908 (sensitivity=75.9%, specificity=90.5%).</p><p><strong>Conclusion: </strong>The wheat BBEA demonstrated greater diagnostic accuracy compared to existing specific IgE tests for wheat allergy.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-16","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}
Background: Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown.
Objective: To describe blood and BM eosinophil characteristics in SM.
Methods: A large collection of BM biopsies was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining, and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence.
Results: Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in non-advanced-SM (n=37 BM biopsies) compared to both controls (n=8, p=0.0003) and to advanced SM (n=24, p=0.014). In non-advanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r=0.38, p=0.038), eosinophils count in BM biopsies (r=0.45, p=0.007), EPX staining (r=0.37, p=0.035) and eosinophil degranulation (r=0.39, p=0.023). Eosinophil counts in BM biopsies also correlated with MC counts (r=0.47, p=0.006) and KIT staining surface (r=0.49, p=0.003). BM MCs expressed interleukin-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils display several increased surface markers compared to controls, suggesting an activated state.
Conclusion: Our data suggest a possible crosstalk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in non-advanced-SM not fully controlled by other therapies.
背景:据报道,在各种过敏性疾病中,嗜酸性粒细胞和肥大细胞(MC)之间存在双向相互作用。骨髓(BM)嗜酸性粒细胞增多在全身性肥大细胞增多症(SM)中很常见,其次是血液嗜酸性粒细胞增多,但其意义尚不清楚:描述系统性肥大细胞增多症患者血液和骨髓嗜酸性粒细胞的特征:方法:使用免疫组化染色和全切片成像技术分析了大量的骨髓活组织切片。嗜酸性粒细胞过氧化物酶(EPX)染色检测嗜酸性粒细胞和细胞外颗粒,KIT染色检测MCs。使用流式细胞术和免疫荧光进行了补充分析:结果:在SM的BM MC浸润内或周围观察到嗜酸性粒细胞浸润和大面积嗜酸性粒细胞脱颗粒。与对照组(8 例,P=0.0003)和晚期 SM(24 例,P=0.014)相比,非晚期 SM(37 例 BM 活检样本)的 EPX 染色表面更高,突出显示完整的嗜酸性粒细胞和嗜酸性粒细胞脱颗粒。在非晚期 SM 中,血清胰蛋白酶水平与生化组织抽吸物中嗜酸性粒细胞计数百分比(斯皮尔曼 r 系数 r=0.38,p=0.038)、生化组织活检中嗜酸性粒细胞计数(r=0.45,p=0.007)、EPX 染色(r=0.37,p=0.035)和嗜酸性粒细胞脱颗粒(r=0.39,p=0.023)之间呈正相关。BM 活检中的嗜酸性粒细胞数量也与 MC 数量(r=0.47,p=0.006)和 KIT 染色表面(r=0.49,p=0.003)相关。BM MCs表达白细胞介素-5受体和其他常见的嗜酸性粒细胞细胞因子/趋化因子受体,与对照组相比,血液中的嗜酸性粒细胞显示出几种增加的表面标记物,这表明嗜酸性粒细胞处于活化状态:我们的数据表明 MCs 和嗜酸性粒细胞之间可能存在串扰,支持 MCs 释放胰蛋白酶和 MCs 活化相关症状。这为其他疗法无法完全控制的非晚期SM患者靶向治疗嗜酸性粒细胞提供了依据。
{"title":"Interactions Between Eosinophils and IL5Rα+ Mast Cells in Non-Advanced Systemic Mastocytosis.","authors":"Guillaume Lefèvre, Jean-Baptiste Gibier, Antonino Bongiovanni, Ludovic Lhermitte, Julien Rossignol, Emilie Anglo, Arnaud Dendooven, Romain Dubois, Louis Terriou, David Launay, Stéphane Barete, Stéphane Esnault, Laurent Frenzel, Clément Gourguechon, Thomas Ballul, Frédéric Dezoteux, Delphine Staumont-Salle, Marie-Christine Copin, Rachel Rignault-Bricard, Thiago Trovati Maciel, Gandhi Damaj, Meryem Tardivel, Marie Crinquette-Verhasselt, Patrice Dubreuil, Leila Maouche-Chrétien, Julie Bruneau, Olivier Lortholary, Nicolas Duployez, Hélène Behal, Thierry Jo Molina, Olivier Hermine","doi":"10.1016/j.jaci.2024.07.025","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.07.025","url":null,"abstract":"<p><strong>Background: </strong>Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown.</p><p><strong>Objective: </strong>To describe blood and BM eosinophil characteristics in SM.</p><p><strong>Methods: </strong>A large collection of BM biopsies was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining, and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence.</p><p><strong>Results: </strong>Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in non-advanced-SM (n=37 BM biopsies) compared to both controls (n=8, p=0.0003) and to advanced SM (n=24, p=0.014). In non-advanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r=0.38, p=0.038), eosinophils count in BM biopsies (r=0.45, p=0.007), EPX staining (r=0.37, p=0.035) and eosinophil degranulation (r=0.39, p=0.023). Eosinophil counts in BM biopsies also correlated with MC counts (r=0.47, p=0.006) and KIT staining surface (r=0.49, p=0.003). BM MCs expressed interleukin-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils display several increased surface markers compared to controls, suggesting an activated state.</p><p><strong>Conclusion: </strong>Our data suggest a possible crosstalk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in non-advanced-SM not fully controlled by other therapies.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995785","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}
Pub Date : 2024-08-14DOI: 10.1016/j.jaci.2024.07.027
Jordan Zeldin, Grace Ratley, Nadia Shobnam, Ian A Myles
Atopic dermatitis (AD) is a complex disease characterized by dry, pruritic skin and significant atopic and psychological sequelae. Although AD has always been viewed as multifactorial, early research was dominated by overlapping genetic determinist views of either innate barrier defects leading to inflammation or innate inflammation eroding skin barrier function. Since 1970, however, the incidence of AD in the United States has increased at a pace that far exceeds genetic drift, thus suggesting a modern, environmental etiology. Another implicated factor is Staphylococcus aureus; however, a highly contagious microorganism is unlikely to be the primary etiology of a noncommunicable disease. Recently, the roles of the skin and gut microbiomes have received greater attention as potentially targetable drivers of AD. Here too, however, dysbiosis on a population scale would require induction by an environmental factor. In this review, we describe the evidence supporting the environmental hypothesis of AD etiology and detail the molecular mechanisms of each of the AD-relevant toxins. We also outline how a pollution-focused paradigm demands earnest engagement with environmental injustice if the field is to meaningfully address racial and geographic disparities. Identifying specific toxins and their mechanisms can also inform in-home and national mitigation strategies.
{"title":"The clinical, mechanistic, and social impacts of air pollution on atopic dermatitis.","authors":"Jordan Zeldin, Grace Ratley, Nadia Shobnam, Ian A Myles","doi":"10.1016/j.jaci.2024.07.027","DOIUrl":"10.1016/j.jaci.2024.07.027","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a complex disease characterized by dry, pruritic skin and significant atopic and psychological sequelae. Although AD has always been viewed as multifactorial, early research was dominated by overlapping genetic determinist views of either innate barrier defects leading to inflammation or innate inflammation eroding skin barrier function. Since 1970, however, the incidence of AD in the United States has increased at a pace that far exceeds genetic drift, thus suggesting a modern, environmental etiology. Another implicated factor is Staphylococcus aureus; however, a highly contagious microorganism is unlikely to be the primary etiology of a noncommunicable disease. Recently, the roles of the skin and gut microbiomes have received greater attention as potentially targetable drivers of AD. Here too, however, dysbiosis on a population scale would require induction by an environmental factor. In this review, we describe the evidence supporting the environmental hypothesis of AD etiology and detail the molecular mechanisms of each of the AD-relevant toxins. We also outline how a pollution-focused paradigm demands earnest engagement with environmental injustice if the field is to meaningfully address racial and geographic disparities. Identifying specific toxins and their mechanisms can also inform in-home and national mitigation strategies.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995786","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}
Pub Date : 2024-08-14DOI: 10.1016/j.jaci.2024.07.026
Claus Bachert, Asif H Khan, Wytske J Fokkens, Claire Hopkins, Philippe Gevaert, Joseph K Han, Peter W Hellings, Stella E Lee, Jérôme Msihid, Scott Nash, Harry Sacks, Juby A Jacob-Nara, Yamo Deniz, Paul J Rowe
Background: Responder analyses of SINUS phase 3 study data have shown clinically meaningful improvements across multiple chronic rhinosinusitis with nasal polyps (CRSwNP) outcomes with dupilumab.
Objective: To gain a better understanding of dupilumab response dynamics over 52 weeks.
Methods: Post hoc analysis using data from the SINUS-52 (NCT02898454) intention-to-treat population, of patients with severe CRSwNP who received dupilumab 300 mg once every 2 weeks (q2w) or placebo. Response, defined as an improvement from baseline of ≥ 1 point for Nasal Polyp Score (NPS), nasal congestion (NC), and loss of smell (LoS), and ≥ 8.9 points for 22-item Sino-Nasal Outcome Test (SNOT-22), was assessed for rapidity, maintenance, and durability.
Results: 303 patients (dupilumab, n = 150; placebo, n = 153) were included. For each outcome measure, a greater proportion of patients achieved first response by Week 16 (rapidity) with dupilumab vs placebo: NPS, 75.3% vs 39.2%; NC, 60.0% vs 24.2%; LoS, 60.7% vs 15.7%; and SNOT-22, 83.3% vs 66.0%. Among dupilumab patients with a response by Week 16, more than 80% maintained response at Week 52 (maintenance). Over 52 weeks, greater proportions of dupilumab patients were responders at ≥ 80% of time points: NPS, 46.7% vs 2.6%; NC, 46.7% vs 9.2%; LoS, 47.3% vs 3.9%; and SNOT-22, 62.0% vs 21.6% (durability).
Conclusion: Most CRSwNP patients achieve clinically meaningful responses to dupilumab by Week 16, and most of these patients had maintenance and durability of response with continued treatment over time.
背景:对SINUS 3期研究数据进行的应答者分析表明,使用dupilumab后,慢性鼻炎伴鼻息肉(CRSwNP)的多种疗效均得到了有临床意义的改善:更好地了解杜必鲁单抗 52 周内的反应动态:方法:利用 SINUS-52 (NCT02898454) 意向治疗人群的数据进行事后分析,研究对象为接受杜必鲁单抗 300 毫克、每两周一次 (q2w) 或安慰剂治疗的严重 CRSwNP 患者。反应的定义是鼻息肉评分(NPS)、鼻塞(NC)和嗅觉减退(LoS)与基线相比改善≥1分,22项鼻功能测试(SNOT-22)改善≥8.9分,并对反应的快速性、维持性和持久性进行评估:共纳入 303 名患者(杜匹单抗,n = 150;安慰剂,n = 153)。在各项结果指标中,使用杜比单抗与安慰剂相比,在第16周(快速性)之前获得首次应答的患者比例更高:NPS,75.3% vs 39.2%;NC,60.0% vs 24.2%;LoS,60.7% vs 15.7%;SNOT-22,83.3% vs 66.0%。在第 16 周出现应答的杜比鲁单抗患者中,超过 80% 的患者在第 52 周(维持期)保持了应答。在52周内,更多的杜匹单抗患者在≥80%的时间点有应答:NPS,46.7% vs 2.6%;NC,46.7% vs 9.2%;LoS,47.3% vs 3.9%;SNOT-22,62.0% vs 21.6%(耐久性):结论:大多数 CRSwNP 患者在第 16 周前对杜匹单抗产生了有临床意义的反应,其中大多数患者的反应在持续治疗后得到了维持和持久。
{"title":"Dupilumab response onset, maintenance, and durability in patients with severe CRSwNP.","authors":"Claus Bachert, Asif H Khan, Wytske J Fokkens, Claire Hopkins, Philippe Gevaert, Joseph K Han, Peter W Hellings, Stella E Lee, Jérôme Msihid, Scott Nash, Harry Sacks, Juby A Jacob-Nara, Yamo Deniz, Paul J Rowe","doi":"10.1016/j.jaci.2024.07.026","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.07.026","url":null,"abstract":"<p><strong>Background: </strong>Responder analyses of SINUS phase 3 study data have shown clinically meaningful improvements across multiple chronic rhinosinusitis with nasal polyps (CRSwNP) outcomes with dupilumab.</p><p><strong>Objective: </strong>To gain a better understanding of dupilumab response dynamics over 52 weeks.</p><p><strong>Methods: </strong>Post hoc analysis using data from the SINUS-52 (NCT02898454) intention-to-treat population, of patients with severe CRSwNP who received dupilumab 300 mg once every 2 weeks (q2w) or placebo. Response, defined as an improvement from baseline of ≥ 1 point for Nasal Polyp Score (NPS), nasal congestion (NC), and loss of smell (LoS), and ≥ 8.9 points for 22-item Sino-Nasal Outcome Test (SNOT-22), was assessed for rapidity, maintenance, and durability.</p><p><strong>Results: </strong>303 patients (dupilumab, n = 150; placebo, n = 153) were included. For each outcome measure, a greater proportion of patients achieved first response by Week 16 (rapidity) with dupilumab vs placebo: NPS, 75.3% vs 39.2%; NC, 60.0% vs 24.2%; LoS, 60.7% vs 15.7%; and SNOT-22, 83.3% vs 66.0%. Among dupilumab patients with a response by Week 16, more than 80% maintained response at Week 52 (maintenance). Over 52 weeks, greater proportions of dupilumab patients were responders at ≥ 80% of time points: NPS, 46.7% vs 2.6%; NC, 46.7% vs 9.2%; LoS, 47.3% vs 3.9%; and SNOT-22, 62.0% vs 21.6% (durability).</p><p><strong>Conclusion: </strong>Most CRSwNP patients achieve clinically meaningful responses to dupilumab by Week 16, and most of these patients had maintenance and durability of response with continued treatment over time.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995784","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}
Pub Date : 2024-08-13DOI: 10.1016/j.jaci.2024.08.002
Maarja Soomann, Viktor Bily, Magdeldin Elgizouli, Dennis Kraemer, Gülfirde Akgül, Horst von Bernuth, Markéta Bloomfield, Nicholas Brodszki, Fabio Candotti, Elisabeth Förster-Waldl, Tomas Freiberger, Maria Giżewska, Adam Klocperk, Uwe Kölsch, Kim E Nichols, Renate Krüger, Ninad Oak, Małgorzata Pac, Seraina Prader, Kjeld Schmiegelow, Anna Šedivá, Georgios Sogkas, Anna Stittrich, Ulrik Kristoffer Stoltze, Katerina Theodoropoulou, Karin Wadt, Melanie Wong, Maximillian Zeyda, Jana Pachlopnik Schmid, Johannes Trück
Background: Agammaglobulinemia due to variants in IGLL1 has traditionally been considered an exceedingly rare form of severe B-cell deficiency, with only eight documented cases in the literature. Surprisingly, the first agammaglobulinemic patient identified by newborn screening (NBS) through quantification of kappa-deleting recombination excision circles harbored variants in IGLL1.
Objective: To provide a comprehensive overview of the clinical and immunological findings of patients with B-cell deficiency attributed to variants in IGLL1.
Methods: NBS programs reporting using kappa-deleting recombination excision circle assays, the European Society for Immunodeficiencies Registry, and authors of published reports featuring patients with B-cell deficiency linked to IGLL1 variants were contacted. Only patients with (likely) pathogenic variants, reduced CD19+ counts and no alternative diagnosis were included.
Results: The study included 13 patients identified through NBS, two clinically diagnosed patients, and two asymptomatic siblings. All had severely reduced CD19+ B-cells (< 0.1×109/L) on first evaluation, yet subsequent follow-ups indicated residual immunoglobulin production. Specific antibody responses to vaccine antigens varied, with a predominant reduction observed during infancy. Clinical outcomes were favorable with immunoglobulin G substitution. Two patients successfully discontinued substitution without developing susceptibility to infections and maintaining immunoglobulin levels. The pooled incidence of homozygous or compound heterozygous pathogenic IGLL1 variants identified by NBS in Austria, Czechia, and Switzerland was 1.3:100´000, almost double of X-linked agammaglobulinemia.
Conclusion: B-cell deficiency resulting from IGLL1 variants appears to be more prevalent than initially believed. Despite markedly low B-cell counts, the clinical course in some patients may be milder than reported in the literature so far.
背景:传统上,IGLL1变异导致的农抗球蛋白血症被认为是一种极为罕见的严重B细胞缺乏症,文献中仅有8例记录在案。令人惊讶的是,第一例通过新生儿筛查(NBS)定量检测卡帕缺失重组切除圈发现的丙种球蛋白血症患者携带 IGLL1 变异:全面概述因 IGLL1 变异而导致 B 细胞缺乏症患者的临床和免疫学结果:方法:我们联系了使用卡帕缺失重组切除圈检测法进行报告的 NBS 项目、欧洲免疫缺陷协会注册中心(European Society for Immunodeficiencies Registry),以及已发表的与 IGLL1 变异有关的 B 细胞缺乏症患者报告的作者。只有具有(可能)致病变体、CD19+计数减少且无其他诊断结果的患者才被纳入研究范围:研究包括 13 名通过 NBS 确定的患者、两名临床诊断患者和两名无症状的兄弟姐妹。首次评估时,所有患者的 CD19+ B 细胞均严重减少(< 0.1×109/L),但随后的随访结果显示仍有免疫球蛋白产生。对疫苗抗原的特异性抗体反应各不相同,主要是在婴儿期出现减少。免疫球蛋白 G 替代的临床效果良好。两名患者成功终止了替代治疗,没有出现感染易感性并保持了免疫球蛋白水平。在奥地利、捷克和瑞士,通过 NBS 发现的同卵或复合杂合致病性 IGLL1 变体的总发病率为 1.3:100´000,几乎是 X 连锁丙种球蛋白血症的两倍:结论:IGLL1 变体导致的 B 细胞缺乏症似乎比最初认为的更为普遍。结论:IGLL1 变体导致的 B 细胞缺乏症似乎比最初认为的更为普遍。尽管 B 细胞计数明显偏低,但一些患者的临床病程可能比迄今为止文献报道的要轻。
{"title":"Variants in IGLL1 cause a broad phenotype from agammaglobulinemia to transient hypogammaglobulinemia.","authors":"Maarja Soomann, Viktor Bily, Magdeldin Elgizouli, Dennis Kraemer, Gülfirde Akgül, Horst von Bernuth, Markéta Bloomfield, Nicholas Brodszki, Fabio Candotti, Elisabeth Förster-Waldl, Tomas Freiberger, Maria Giżewska, Adam Klocperk, Uwe Kölsch, Kim E Nichols, Renate Krüger, Ninad Oak, Małgorzata Pac, Seraina Prader, Kjeld Schmiegelow, Anna Šedivá, Georgios Sogkas, Anna Stittrich, Ulrik Kristoffer Stoltze, Katerina Theodoropoulou, Karin Wadt, Melanie Wong, Maximillian Zeyda, Jana Pachlopnik Schmid, Johannes Trück","doi":"10.1016/j.jaci.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.08.002","url":null,"abstract":"<p><strong>Background: </strong>Agammaglobulinemia due to variants in IGLL1 has traditionally been considered an exceedingly rare form of severe B-cell deficiency, with only eight documented cases in the literature. Surprisingly, the first agammaglobulinemic patient identified by newborn screening (NBS) through quantification of kappa-deleting recombination excision circles harbored variants in IGLL1.</p><p><strong>Objective: </strong>To provide a comprehensive overview of the clinical and immunological findings of patients with B-cell deficiency attributed to variants in IGLL1.</p><p><strong>Methods: </strong>NBS programs reporting using kappa-deleting recombination excision circle assays, the European Society for Immunodeficiencies Registry, and authors of published reports featuring patients with B-cell deficiency linked to IGLL1 variants were contacted. Only patients with (likely) pathogenic variants, reduced CD19+ counts and no alternative diagnosis were included.</p><p><strong>Results: </strong>The study included 13 patients identified through NBS, two clinically diagnosed patients, and two asymptomatic siblings. All had severely reduced CD19+ B-cells (< 0.1×10<sup>9</sup>/L) on first evaluation, yet subsequent follow-ups indicated residual immunoglobulin production. Specific antibody responses to vaccine antigens varied, with a predominant reduction observed during infancy. Clinical outcomes were favorable with immunoglobulin G substitution. Two patients successfully discontinued substitution without developing susceptibility to infections and maintaining immunoglobulin levels. The pooled incidence of homozygous or compound heterozygous pathogenic IGLL1 variants identified by NBS in Austria, Czechia, and Switzerland was 1.3:100´000, almost double of X-linked agammaglobulinemia.</p><p><strong>Conclusion: </strong>B-cell deficiency resulting from IGLL1 variants appears to be more prevalent than initially believed. Despite markedly low B-cell counts, the clinical course in some patients may be milder than reported in the literature so far.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987946","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}
Pub Date : 2024-08-13DOI: 10.1016/j.jaci.2024.07.024
Fabian Bick, Claudia M Brenis Gómez, Inés Lammens, Justine Van Moorleghem, Caroline De Wolf, Sam Dupont, Laure Dumoutier, Neal P Smith, Alexandra-Chloé Villani, Robin Browaeys, Jehan Alladina, Alexis M Haring, Benjamin D Medoff, Josalyn L Cho, René Bigirimana, Joao Vieira, Hamida Hammad, Christophe Blanchetot, Martijn J Schuijs, Bart N Lambrecht
Background: Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5 and IL-13 cytokines produced by TH2 lymphocytes or type 2 innate lymphoid cells (ILC2s). Interleukin-2 family cytokines play a key role in the differentiation, homeostasis and effector function of innate and adaptive lymphocytes.
Objective: IL-9 and IL-21 boost the activation and proliferation of TH2 and ILC2s, but the relative importance and potential synergism between these γc cytokines is currently unknown.
Methods: Using newly generated antibodies, we inhibited IL-9 and IL-21 alone or in combination, in various murine models of asthma. In a translational approach using segmental allergen challenge, we recently described elevated IL-9 levels in human allergic asthmatics in comparison to non-asthmatic controls. Here, we also measured IL-21 in both groups.
Results: IL-9 played a central role in controlling innate IL-33 induced lung inflammation by promoting proliferation and activation of ILC2s, in an IL-21 independent manner. Conversely, chronic house dust mite induced airway inflammation, mainly driven by adaptive immunity, was solely dependent on IL-21, that controlled TH2 activation, eosinophilia, total serum IgE and formation of tertiary lymphoid structures. In a model of innate on adaptive immunity driven by papain allergen, a clear synergy was found between both pathways, since combined anti-IL-9 or anti-IL-21 blockade was superior in reducing key asthma features. In human bronchoalveolar lavage (BAL) samples we measured elevated IL-21 protein within the allergic asthmatic group, compared with the allergic control group. We also found increased IL21R transcripts and predicted IL-21 ligand activity in various disease-associated cell subsets.
Conclusion: IL-9 and IL-21 play important and non-redundant roles in allergic asthma by boosting ILC2s and TH2 cells, revealing a dual IL-9 and IL-21 targeting strategy as a new and testable approach.
{"title":"Interleukin-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.","authors":"Fabian Bick, Claudia M Brenis Gómez, Inés Lammens, Justine Van Moorleghem, Caroline De Wolf, Sam Dupont, Laure Dumoutier, Neal P Smith, Alexandra-Chloé Villani, Robin Browaeys, Jehan Alladina, Alexis M Haring, Benjamin D Medoff, Josalyn L Cho, René Bigirimana, Joao Vieira, Hamida Hammad, Christophe Blanchetot, Martijn J Schuijs, Bart N Lambrecht","doi":"10.1016/j.jaci.2024.07.024","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.07.024","url":null,"abstract":"<p><strong>Background: </strong>Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5 and IL-13 cytokines produced by T<sub>H</sub>2 lymphocytes or type 2 innate lymphoid cells (ILC2s). Interleukin-2 family cytokines play a key role in the differentiation, homeostasis and effector function of innate and adaptive lymphocytes.</p><p><strong>Objective: </strong>IL-9 and IL-21 boost the activation and proliferation of T<sub>H</sub>2 and ILC2s, but the relative importance and potential synergism between these γc cytokines is currently unknown.</p><p><strong>Methods: </strong>Using newly generated antibodies, we inhibited IL-9 and IL-21 alone or in combination, in various murine models of asthma. In a translational approach using segmental allergen challenge, we recently described elevated IL-9 levels in human allergic asthmatics in comparison to non-asthmatic controls. Here, we also measured IL-21 in both groups.</p><p><strong>Results: </strong>IL-9 played a central role in controlling innate IL-33 induced lung inflammation by promoting proliferation and activation of ILC2s, in an IL-21 independent manner. Conversely, chronic house dust mite induced airway inflammation, mainly driven by adaptive immunity, was solely dependent on IL-21, that controlled T<sub>H</sub>2 activation, eosinophilia, total serum IgE and formation of tertiary lymphoid structures. In a model of innate on adaptive immunity driven by papain allergen, a clear synergy was found between both pathways, since combined anti-IL-9 or anti-IL-21 blockade was superior in reducing key asthma features. In human bronchoalveolar lavage (BAL) samples we measured elevated IL-21 protein within the allergic asthmatic group, compared with the allergic control group. We also found increased IL21R transcripts and predicted IL-21 ligand activity in various disease-associated cell subsets.</p><p><strong>Conclusion: </strong>IL-9 and IL-21 play important and non-redundant roles in allergic asthma by boosting ILC2s and T<sub>H</sub>2 cells, revealing a dual IL-9 and IL-21 targeting strategy as a new and testable approach.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987945","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}
Pub Date : 2024-08-12DOI: 10.1016/j.jaci.2024.06.024
Moritz Maximilian Hollstein, Stephan Traidl, Anne Heetfeld, Susann Forkel, Andreas Leha, Natalia Alkon, Jannik Ruwisch, Christof Lenz, Michael Peter Schön, Martin Schmelz, Patrick Brunner, Martin Steinhoff, Timo Buhl
Background: Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data.
Objective: We characterized lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis.
Methods: Skin microdialysis samples from patients with atopic dermatitis (AD, n = 6), psoriasis vulgaris (PSO, n = 7), or prurigo nodularis (PN, n = 6), as well as healthy controls (n = 7), were subjected to proteomic and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines.
Results: Among the top 20 enriched Gene Ontology (GO; geneontology.org) annotations, nicotinamide adenine dinucleotide metabolic process, regulation of secretion by cell, and pyruvate metabolic process were elevated in microdialysates from lesional AD skin compared with both nonlesional skin and controls. The top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG; genome.jp/kegg) pathways in these 3 groups overlapped almost completely. In contrast, nonlesional skin from patients with PSO or PN and control skin showed no overlap with lesional skin in this KEGG pathway analysis. Lesional skin from patients with PSO, but not AD or PN, showed significantly elevated protein levels of MCP-1 compared with nonlesional skin. IL-8 was elevated in lesional versus nonlesional AD and PSO skin, whereas IL-12p40 and IL-22 were higher only in lesional PSO skin. Integrated single-cell RNA sequencing data revealed identical cellular sources of these cytokines in AD, PSO, and PN.
Conclusion: On the basis of microdialysates, the proteomic data of lesional PSO and PN skin, but not lesional AD skin, differed significantly from those of nonlesional skin. IL-8, IL-22, MCP-1, and IL-12p40 might be suitable markers for minimally invasive molecular profiling.
背景:由于缺乏足够的原位数据,对炎症性皮肤病的病理生理学,尤其是蛋白质组水平的深入研究受到严重阻碍:利用皮肤微透析技术描述炎症性皮肤病的病变和非病变皮肤的特征:对特应性皮炎(AD,n=6)、寻常型银屑病(PSO,n=7)或结节性瘙痒症(PN,n=6)患者以及健康对照组(n=7)的皮肤微透析样本进行蛋白质组学和多重细胞因子分析。皮肤活检标本的单细胞RNA测序用于确定细胞因子的细胞来源:结果:与非病变皮肤和对照组相比,在前 20 个富集的 GO 注释中,NAD 代谢过程、细胞分泌调控和丙酮酸代谢过程在病变 AD 皮肤的微量透析液中含量升高。这三类患者的前 20 条 KEGG 通路几乎完全重叠。相比之下,PSO 或 PN 患者的非病变皮肤和对照组皮肤在 KEGG 通路分析中与病变皮肤没有重叠。与非皮损皮肤相比,PSO 患者的皮损皮肤,而非 AD 或 PN 患者的皮损皮肤的 MCP-1 蛋白水平明显升高。IL-8在病变与非病变AD和PSO皮肤中均有升高,而IL-12p40和IL-22仅在病变PSO皮肤中升高。综合单细胞 RNA-seq 数据显示,这些细胞因子在 AD、PSO 和 PN 中的细胞来源相同:结论:基于微量电解质,病变 PSO 和 PN 皮肤(而非病变 AD 皮肤)的蛋白质组数据与非病变皮肤有显著差异。IL-8、IL-22、MCP-1和IL-12p40可能是微创分子分析的合适标记物。
{"title":"Skin microdialysis detects distinct immunologic patterns in chronic inflammatory skin diseases.","authors":"Moritz Maximilian Hollstein, Stephan Traidl, Anne Heetfeld, Susann Forkel, Andreas Leha, Natalia Alkon, Jannik Ruwisch, Christof Lenz, Michael Peter Schön, Martin Schmelz, Patrick Brunner, Martin Steinhoff, Timo Buhl","doi":"10.1016/j.jaci.2024.06.024","DOIUrl":"10.1016/j.jaci.2024.06.024","url":null,"abstract":"<p><strong>Background: </strong>Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data.</p><p><strong>Objective: </strong>We characterized lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis.</p><p><strong>Methods: </strong>Skin microdialysis samples from patients with atopic dermatitis (AD, n = 6), psoriasis vulgaris (PSO, n = 7), or prurigo nodularis (PN, n = 6), as well as healthy controls (n = 7), were subjected to proteomic and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines.</p><p><strong>Results: </strong>Among the top 20 enriched Gene Ontology (GO; geneontology.org) annotations, nicotinamide adenine dinucleotide metabolic process, regulation of secretion by cell, and pyruvate metabolic process were elevated in microdialysates from lesional AD skin compared with both nonlesional skin and controls. The top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG; genome.jp/kegg) pathways in these 3 groups overlapped almost completely. In contrast, nonlesional skin from patients with PSO or PN and control skin showed no overlap with lesional skin in this KEGG pathway analysis. Lesional skin from patients with PSO, but not AD or PN, showed significantly elevated protein levels of MCP-1 compared with nonlesional skin. IL-8 was elevated in lesional versus nonlesional AD and PSO skin, whereas IL-12p40 and IL-22 were higher only in lesional PSO skin. Integrated single-cell RNA sequencing data revealed identical cellular sources of these cytokines in AD, PSO, and PN.</p><p><strong>Conclusion: </strong>On the basis of microdialysates, the proteomic data of lesional PSO and PN skin, but not lesional AD skin, differed significantly from those of nonlesional skin. IL-8, IL-22, MCP-1, and IL-12p40 might be suitable markers for minimally invasive molecular profiling.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982372","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}
Pub Date : 2024-08-10DOI: 10.1016/j.jaci.2024.07.023
Ahmed Kabil, Natalia Nayyar, Julyanne Brassard, Yicong Li, Sameeksha Chopra, Michael R Hughes, Kelly M McNagny
Background: The abundance and diversity of intestinal commensal bacteria influence systemic immunity with impact on disease susceptibility and severity. For example, loss of short chain fatty acid (SCFA)-fermenting bacteria in early life (humans and mice) is associated with enhanced type 2 immune responses in peripheral tissues including the lung.
Objective: Our goal was to reveal the microbiome-dependent cellular and molecular mechanisms driving enhanced susceptibility to type 2 allergic lung disease.
Methods: We used low-dose vancomycin to selectively deplete SCFA-fermenting bacteria in wild-type mice. We then examined the frequency and activation status of innate and adaptive immune cell lineages with and without SCFA supplementation. Finally, we used ILC2-deficient and signal transducer and activator of transcription 6 (STAT6)-deficient transgenic mouse strains to delineate the cellular and cytokine pathways leading to enhanced allergic disease susceptibility.
Results: Mice with vancomycin-induced dysbiosis exhibited a 2-fold increase in lung ILC2 primed to produce elevated levels of IL-2, -5, and -13. In addition, upon IL-33 inhalation, mouse lung ILC2 displayed a novel ability to produce high levels of IL-4. These expanded and primed ILC2s drove B1 cell expansion and IL-4-dependent production of IgE that in turn led to exacerbated allergic inflammation. Importantly, these enhanced lung inflammatory phenotypes in mice with vancomycin-induced dysbiosis were reversed by administration of dietary SCFA (specifically butyrate).
Conclusion: SCFAs regulate an ILC2-B1 cell-IgE axis. Early-life administration of vancomycin, an antibiotic known to deplete SCFA-fermenting gut bacteria, primes and amplifies this axis and leads to lifelong enhanced susceptibility to type 2 allergic lung disease.
{"title":"Microbial intestinal dysbiosis drives long-term allergic susceptibility by sculpting an ILC2-B1 cell-innate IgE axis.","authors":"Ahmed Kabil, Natalia Nayyar, Julyanne Brassard, Yicong Li, Sameeksha Chopra, Michael R Hughes, Kelly M McNagny","doi":"10.1016/j.jaci.2024.07.023","DOIUrl":"10.1016/j.jaci.2024.07.023","url":null,"abstract":"<p><strong>Background: </strong>The abundance and diversity of intestinal commensal bacteria influence systemic immunity with impact on disease susceptibility and severity. For example, loss of short chain fatty acid (SCFA)-fermenting bacteria in early life (humans and mice) is associated with enhanced type 2 immune responses in peripheral tissues including the lung.</p><p><strong>Objective: </strong>Our goal was to reveal the microbiome-dependent cellular and molecular mechanisms driving enhanced susceptibility to type 2 allergic lung disease.</p><p><strong>Methods: </strong>We used low-dose vancomycin to selectively deplete SCFA-fermenting bacteria in wild-type mice. We then examined the frequency and activation status of innate and adaptive immune cell lineages with and without SCFA supplementation. Finally, we used ILC2-deficient and signal transducer and activator of transcription 6 (STAT6)-deficient transgenic mouse strains to delineate the cellular and cytokine pathways leading to enhanced allergic disease susceptibility.</p><p><strong>Results: </strong>Mice with vancomycin-induced dysbiosis exhibited a 2-fold increase in lung ILC2 primed to produce elevated levels of IL-2, -5, and -13. In addition, upon IL-33 inhalation, mouse lung ILC2 displayed a novel ability to produce high levels of IL-4. These expanded and primed ILC2s drove B1 cell expansion and IL-4-dependent production of IgE that in turn led to exacerbated allergic inflammation. Importantly, these enhanced lung inflammatory phenotypes in mice with vancomycin-induced dysbiosis were reversed by administration of dietary SCFA (specifically butyrate).</p><p><strong>Conclusion: </strong>SCFAs regulate an ILC2-B1 cell-IgE axis. Early-life administration of vancomycin, an antibiotic known to deplete SCFA-fermenting gut bacteria, primes and amplifies this axis and leads to lifelong enhanced susceptibility to type 2 allergic lung disease.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971178","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}
Pub Date : 2024-08-06DOI: 10.1016/j.jaci.2024.08.001
Ayobami Akenroye, Christopher Hvisdas, Jessica Stern, John W Jackson, Margee Louisias
Background: There are pre-existing inequities in asthma care.
Objectives: We sought to evaluate effect modification by race of the effect of insurance on biologic therapy use in patients with asthma and related diseases.
Methods: We conducted inverse probability weighted analyses using electronic health records data from 2011 to 2020 from a large health care system in Boston, Mass. We evaluated the odds of not initiating omalizumab or mepolizumab therapy within 1 year of prescription for an approved indication.
Results: We identified 1132 individuals who met study criteria. Twenty-seven percent of these patients had public insurance and 12% belonged to a historically marginalized group (HMG). One-quarter of patients did not initiate the prescribed biologic. Among patients with asthma, individuals belonging to HMG had higher exacerbation rates in the period before initiation compared to non-HMG individuals, regardless of insurance type. Among HMG patients with asthma, those with private insurance were less likely to not initiate therapy compared to those with public insurance (odds ratio [OR]: 0.67, and 95% CI: 0.56-0.79). Among non-HMG with asthma, privately insured and publicly insured individuals had similar rates of not initiating the prescribed biologic (OR: 1.02; 95% CI: 0.95-1.09). Among those publicly insured with asthma, HMGs had higher odds of not initiating therapy compared to non-HMGs (OR: 1.16; 95% CI: 1.03-1.31), but privately insured HMG and non-HMG did not differ significantly (OR: 0.99; 95% CI: 0.91-1.07).
Conclusions: Publicly insured individuals belonging to HMG are less likely to initiate biologics when prescribed despite having more severe asthma, while there are no inequities by insurance in individuals belonging to other groups.
{"title":"Race and ethnicity, not just insurance, is associated with biologics initiation in asthma and related conditions.","authors":"Ayobami Akenroye, Christopher Hvisdas, Jessica Stern, John W Jackson, Margee Louisias","doi":"10.1016/j.jaci.2024.08.001","DOIUrl":"10.1016/j.jaci.2024.08.001","url":null,"abstract":"<p><strong>Background: </strong>There are pre-existing inequities in asthma care.</p><p><strong>Objectives: </strong>We sought to evaluate effect modification by race of the effect of insurance on biologic therapy use in patients with asthma and related diseases.</p><p><strong>Methods: </strong>We conducted inverse probability weighted analyses using electronic health records data from 2011 to 2020 from a large health care system in Boston, Mass. We evaluated the odds of not initiating omalizumab or mepolizumab therapy within 1 year of prescription for an approved indication.</p><p><strong>Results: </strong>We identified 1132 individuals who met study criteria. Twenty-seven percent of these patients had public insurance and 12% belonged to a historically marginalized group (HMG). One-quarter of patients did not initiate the prescribed biologic. Among patients with asthma, individuals belonging to HMG had higher exacerbation rates in the period before initiation compared to non-HMG individuals, regardless of insurance type. Among HMG patients with asthma, those with private insurance were less likely to not initiate therapy compared to those with public insurance (odds ratio [OR]: 0.67, and 95% CI: 0.56-0.79). Among non-HMG with asthma, privately insured and publicly insured individuals had similar rates of not initiating the prescribed biologic (OR: 1.02; 95% CI: 0.95-1.09). Among those publicly insured with asthma, HMGs had higher odds of not initiating therapy compared to non-HMGs (OR: 1.16; 95% CI: 1.03-1.31), but privately insured HMG and non-HMG did not differ significantly (OR: 0.99; 95% CI: 0.91-1.07).</p><p><strong>Conclusions: </strong>Publicly insured individuals belonging to HMG are less likely to initiate biologics when prescribed despite having more severe asthma, while there are no inequities by insurance in individuals belonging to other groups.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906692","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}
Pub Date : 2024-08-05DOI: 10.1016/j.jaci.2024.07.022
Benjamin L Wright, Juan Pablo Abonia, Edsel M Abud, Seema S Aceves, Steven J Ackerman, Melinda Braskett, Joy W Chang, Mirna Chehade, Gregory M Constantine, Carla M Davis, Evan S Dellon, Alfred D Doyle, Raquel Durban, David A Hill, Elizabeth T Jensen, Anupama Kewalramani, Paneez Khoury, Amy D Klion, Leah Kottyan, Fei Li Kuang, Emily C McGowan, Melanie A Ruffner, Lisa A Spencer, Jonathan M Spergel, Amiko M Uchida, Joshua B Wechsler, Robert D Pesek
The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.
{"title":"Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting.","authors":"Benjamin L Wright, Juan Pablo Abonia, Edsel M Abud, Seema S Aceves, Steven J Ackerman, Melinda Braskett, Joy W Chang, Mirna Chehade, Gregory M Constantine, Carla M Davis, Evan S Dellon, Alfred D Doyle, Raquel Durban, David A Hill, Elizabeth T Jensen, Anupama Kewalramani, Paneez Khoury, Amy D Klion, Leah Kottyan, Fei Li Kuang, Emily C McGowan, Melanie A Ruffner, Lisa A Spencer, Jonathan M Spergel, Amiko M Uchida, Joshua B Wechsler, Robert D Pesek","doi":"10.1016/j.jaci.2024.07.022","DOIUrl":"10.1016/j.jaci.2024.07.022","url":null,"abstract":"<p><p>The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901846","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}