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Relationship between the outcome of low-dose egg oral immunotherapy and the fold-difference levels of allergen-specific IgE and IgG4 in serum. 低剂量鸡蛋口服免疫疗法的疗效与血清中过敏原特异性 IgE 和 IgG4 的折差水平之间的关系。
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-03-01 DOI: 10.12932/AP-100620-0877
Akihiro Maeta, Yuri Takaoka, Makoto Kameda, Kyoko Takahashi

Background: There are no indices to monitor desensitization by low-dose egg oral immunotherapy (eOIT).

Objective: We aimed to examine the relationship between desensitization by low-dose eOIT and the changes in allergen-specific immunoglobulin E (IgE) and IgG4 levels.

Methods: We carried out low-dose eOIT in 31 patients with severe egg allergy in our previous two studies. After 4 months of treatment, the patients with no observed allergic symptoms in response to the open hard-boiled egg white challenge tests were classified as the negative group, and the remaining patients, the positive group. The fold-difference levels were calculated using 10 Log (Titer after eOIT/Titer before eOIT).

Results: The 28 patients who completed eOIT with sufficient serum collected before and after eOIT were analyzed. The median fold-difference levels of ovomucoid-specific IgE in the negative and positive groups were 0.819 and 0.953, respectively (P = 0.082). The median fold-difference levels of ovalbumin-specific IgG4 in the negative and positive groups were 2.01 and 1.29, respectively (P = 0.057). In the receiver-operating characteristic curves, the area under the curves of fold-difference ovomucoid-specific IgE and ovalbumin-specific IgG4 were 0.701 and 0.719, respectively. The challenge positive predictive values of fold-difference ovomucoid-specific IgE and ovalbumin-specific IgG4 were 83.8% (cut-off point: 0.934) and 77.8% (cut-off point: 1.87), respectively. Moreover, the challenge positive predictive value in patients with both 0.934 < ovomucoid-specific IgE and ovalbumin-specific IgG4 <1.87 was 100%.

Conclusions: The fold-difference levels of allergen-specific IgE and IgG4 in serum are considered useful for monitoring desensitization by low-dose OIT.

背景:目前还没有监测低剂量鸡蛋口服免疫疗法(eOIT)脱敏的指标:目前还没有监测低剂量鸡蛋口服免疫疗法(eOIT)脱敏情况的指标:我们旨在研究低剂量 eOIT 脱敏与过敏原特异性免疫球蛋白 E (IgE) 和 IgG4 水平变化之间的关系:我们在前两项研究中对 31 例严重鸡蛋过敏患者进行了低剂量 eOIT 治疗。治疗 4 个月后,将对开放式煮蛋白挑战试验未观察到过敏症状的患者列为阴性组,其余患者列为阳性组。折差水平用 10 Log(eOIT 后的滴度/eOIT 前的滴度)计算:结果:对完成 eOIT 并在 eOIT 前后采集了足够血清的 28 名患者进行了分析。阴性组和阳性组绒毛膜特异性 IgE 的中位折差水平分别为 0.819 和 0.953(P = 0.082)。阴性组和阳性组卵白蛋白特异性 IgG4 的中位折差水平分别为 2.01 和 1.29(P = 0.057)。在接受者操作特征曲线中,卵清蛋白特异性 IgE 和卵清蛋白特异性 IgG4 的折差曲线下面积分别为 0.701 和 0.719。折差卵清蛋白特异性 IgE 和卵清蛋白特异性 IgG4 的挑战阳性预测值分别为 83.8%(截断点:0.934)和 77.8%(截断点:1.87)。此外,0.934<卵清蛋白特异性 IgE 和卵清蛋白特异性 IgG4 患者的挑战阳性预测值均为 0.934<卵清蛋白特异性 IgE 和卵清蛋白特异性 IgG4:血清中过敏原特异性 IgE 和 IgG4 的折差水平可用于监测低剂量 OIT 的脱敏情况。
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引用次数: 0
Novel variants in CIITA caused type II bare lymphocyte syndrome: A case report. CIITA 中的新变体导致 II 型裸淋巴细胞综合征:病例报告
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-03-01 DOI: 10.12932/AP-020720-0898
Yi Zhang, Yuko Yokoyama, Yanrong Qing, Cong Han, Jiayi Zhu, Tingting Yu, Lei Yin, Ruen Yao, Jian Wang

Background: Type II bare lymphocyte syndrome (BLS II) group A is a rare primary severe immunodeficiency caused by defects in CIITA, one of genes encoding transcriptional regulatory factors for MHC II molecules.

Objective: To report a Chinese boy with mutation of CIITA.

Methods: By reviewing the clinical data of the child and performing a literature search of BLS II group A.

Results: The patient was presented with persistent pneumonia, chronic diarrhea, urinary tract infection, rash, failure to thrive and special facial characteristics. The patient carried novel mutations in CIITA (c.1243delC, p.R415fs*2 and c.3226C>T, p.R1076W) which were identified by next-generation sequencing and confirmed by Sanger sequencing.

Conclusions: This study found novel mutations in the CIITA gene of BLS II, which complemented the mutation spectrum and contributed to the diagnosis, treatment, genetic counseling and prenatal diagnosis of BLS II.

背景:A 组 II 型裸淋巴细胞综合征(BLS II)是一种罕见的原发性重症免疫缺陷病,由编码 MHC II 分子转录调控因子的基因之一 CIITA 的缺陷引起:报告一名患有 CIITA 基因突变的中国男童:方法:回顾患儿的临床资料,并对 BLS II A 组进行文献检索:结果:患儿表现为持续性肺炎、慢性腹泻、尿路感染、皮疹、发育不良和特殊面容。该患者携带 CIITA 的新型突变(c.1243delC,p.R415fs*2 和 c.3226C>T,p.R1076W),这些突变经新一代测序鉴定,并经桑格测序确认:本研究在 BLS II 的 CIITA 基因中发现了新的突变,补充了突变谱,有助于 BLS II 的诊断、治疗、遗传咨询和产前诊断。
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引用次数: 0
Diving deep into fish allergen immunotherapy: Current knowledge and future directions. 深入研究鱼过敏原免疫疗法:当前知识和未来方向。
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-03-01 DOI: 10.12932/AP-030923-1687
Kavita Reginald, Kashaf Nadeem, Ervin Zheng Yang Yap, Amir Hamzah Abdul Latiff

Fish allergy is one of the "big nine" categories of food allergens worldwide, and its prevalence is increasing with the higher demand for this nutritious food source. Fish allergies are a significant health concern as it is a leading cause of food anaphylaxis, accounting for 9% of all deaths from anaphylaxis. The gaps in treating fish allergies at present are the incomplete identification of fish allergens, lack of component-resolved diagnosis of fish allergens in the clinical setting, and the variability in sensitization profiles based on different fish consumption practices. Allergen immunotherapy (AIT) improves tolerance towards accidental consumption of fish and is longer lasting than pharmacotherapy. Current practice or research of fish AIT ranges from the use of whole fish via oral desensitization, to the use of purified recombinant parvalbumin and its hypoallergenic variant, passive IgG immunization, and modifying the allergenicity of parvalbumin by changing the diet of farmed fish. However, the focus of fish allergen-based studies in the context of AIT has been restricted to parvalbumins. More research is required to understand the involvement of other fish allergens, and several other strategies of AIT including peptide vaccines, DNA vaccines, hybrid allergens, and the use of nanobodies that have the capacity to treat multiple allergens have been proposed. For AIT, other important aspects to consider are the route of desensitization, and the biomarkers to assess the success of immunotherapy. Finally, we also address several clinical considerations for fish AIT.

鱼过敏是全球 "九大 "食物过敏原之一,随着人们对这种营养丰富的食物需求量的增加,鱼过敏的发病率也在不断上升。鱼过敏是一个重大的健康问题,因为它是食物过敏性休克的主要原因,占过敏性休克死亡总数的 9%。目前在治疗鱼过敏方面存在的不足是鱼过敏原的鉴定不完全、临床环境中缺乏对鱼过敏原成分的诊断,以及不同鱼类消费习惯导致的过敏特征的差异。过敏原免疫疗法(AIT)可改善对意外食用鱼类的耐受性,而且比药物疗法更持久。目前鱼类过敏原免疫疗法的实践或研究包括通过口服脱敏法使用整条鱼、使用纯化重组副卵白蛋白及其低过敏性变体、被动 IgG 免疫以及通过改变养殖鱼类的饮食来改变副卵白蛋白的过敏性。然而,基于鱼过敏原的 AIT 研究重点仅限于副卵白蛋白。要了解其他鱼类过敏原的参与情况,还需要进行更多的研究,而且还提出了其他几种 AIT 策略,包括肽疫苗、DNA 疫苗、混合过敏原以及使用可治疗多种过敏原的纳米抗体。对于 AIT 而言,需要考虑的其他重要方面包括脱敏途径和评估免疫疗法成功与否的生物标志物。最后,我们还讨论了鱼类 AIT 的几个临床考虑因素。
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引用次数: 0
Killer cell immunoglobulin-like receptors in Thai patients with multiple myeloma. 泰国多发性骨髓瘤患者的杀伤细胞免疫球蛋白样受体。
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-03-01 DOI: 10.12932/AP-130520-0842
Aphiradee Theeranawakam, Sasijit Vejbaesya, Archrob Khuhapinant, Pradermchai Sae-Tam

Background: Natural killer (NK) cells have been implicated in the immune response against multiple myeloma (MM) cells. Killer cell immunoglobulin-like receptors (KIRs) regulate NK cell activity by recognizing specific human leukocyte antigen (HLA) class I as ligands.

Objective: To investigate the association of KIR genes and ligands with MM in the Thai population.

Methods: KIR gene polymorphisms and their HLA ligands were investigated in 66 Thai patients with MM and 200 healthy controls.

Results: The frequencies of KIR3DL1 and 2DS4 were significantly lower in myeloma patients than in controls (P = 0.02). The frequencies of KIR3DL1, 2DS4, 2DL1 with C2, and 3DL1 with Bw4 were significantly higher in the patients achieving > very good partial response (VGPR) than those achieving ≤ VGPR after treatment with bortezomib (P = 0.009, 0.009, 0.01, and 0.02, respectively).

Conclusions: This study suggests the association of KIR genes with the protection against MM and the association of inhibitory KIR and ligands with the response to treatment in MM.

背景:自然杀伤(NK)细胞与针对多发性骨髓瘤(MM)细胞的免疫反应有关。杀伤细胞免疫球蛋白样受体(KIR)通过识别作为配体的特异性人类白细胞抗原(HLA)I类来调节NK细胞的活性:研究泰国人群中 KIR 基因和配体与 MM 的关系:方法:在 66 名泰国 MM 患者和 200 名健康对照者中调查 KIR 基因多态性及其 HLA 配体:结果:骨髓瘤患者 KIR3DL1 和 2DS4 的频率明显低于对照组(P = 0.02)。KIR3DL1、2DS4、2DL1与C2和3DL1与Bw4的频率在硼替佐米治疗后达到>很好部分反应(VGPR)的患者中明显高于达到≤VGPR的患者(P分别为0.009、0.009、0.01和0.02):这项研究表明,KIR 基因与 MM 的保护作用有关,而抑制性 KIR 和配体与 MM 的治疗反应有关。
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引用次数: 0
Inhibitory effect of Zingiber cassumunar Roxb. (Phlai) on nasal cytokine productions and eosinophilic recruitment in patients with allergic rhinitis. 黄芩对过敏性鼻炎患者鼻腔细胞因子分泌和嗜酸性粒细胞聚集的抑制作用
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-03-01 DOI: 10.12932/AP-241022-1486
Nitchanan Achararit, Phuntila Tharabenjasin, Prapasri Kulalert, Paskorn Sritipsukho, Sira Nanthapisal, Noel Pabalan, Nateetip Krishnamra, Panan Suntornsaratoon, Orapan Poachanukoon

Background: Zingiber cassumunar Roxb. (Phlai) has been used for the treatment of allergies including allergic rhinitis (AR). Although the anti-histamine effects have been reported, assessment of nasal cytokine and eosinophil production had not been investigated.

Objective: This study aimed to examine the effect of Phlai on alterations in nasal pro-inflammatory cytokine levels and eosinophil counts in nasal mucosa.

Methods: This was a randomized, double-blind, three-way crossover study. Nasal concentrations of cytokines, namely interleukin (IL)-4, IL-5, IL-13 and interferron-gamma (IFN-γ), nasal smear eosinophilia as well as total nasal symptom score (TNSS) were evaluated before and after a 4 weeks treatment with 200 mg Phlai capsules or placebo in 30 AR patients.

Results: We observed significant (p < 0.05) reduction in IL-5, IL-13 as well as the number of eosinophils in subjects given Phlai. The degree of improvement of TNSS after Phlai treatment was initially manifested in week 2 with the greatest effect in week 4. In contrast, there were no significant differences in all nasal cytokines, eosinophil counts or TNSS between before and after receiving placebo.

Conclusions: These findings provided the first evidence for the anti-allergic effect of Phlai which possibly involved inhibition of nasal pro-inflammatory cytokines production and eosinophilic recruitment. Phlai thus represents a promising herbal medicine for alleviating inflammation and AR symptoms.

背景:黄芩(Zingiber cassumunar Roxb.)一直被用于治疗过敏症,包括过敏性鼻炎(AR)。虽然已有抗组胺作用的报道,但尚未对鼻腔细胞因子和嗜酸性粒细胞的产生进行评估:本研究旨在探讨普莱对鼻粘膜促炎细胞因子水平和嗜酸性粒细胞数量变化的影响:这是一项随机、双盲、三向交叉研究。方法:这是一项随机、双盲、三向交叉研究,对 30 名 AR 患者在服用 200 毫克普莱胶囊或安慰剂 4 周前后的鼻腔细胞因子(即白细胞介素 (IL)-4、IL-5、IL-13 和干扰素-γ (IFN-γ))浓度、鼻腔涂片嗜酸性粒细胞以及鼻腔症状总评分(TNSS)进行了评估:结果:我们观察到服用普莱的受试者的IL-5、IL-13和嗜酸性粒细胞数量明显减少(p < 0.05)。治疗后 TNSS 的改善程度在第 2 周开始显现,第 4 周效果最佳。相比之下,所有鼻腔细胞因子、嗜酸性粒细胞计数或 TNSS 在服用安慰剂前后均无明显差异:这些研究结果首次证明了蓬莱的抗过敏作用,这种作用可能涉及抑制鼻腔促炎细胞因子的产生和嗜酸性粒细胞的聚集。因此,蓬莱是一种很有前景的缓解炎症和 AR 症状的草药。
{"title":"Inhibitory effect of Zingiber cassumunar Roxb. (Phlai) on nasal cytokine productions and eosinophilic recruitment in patients with allergic rhinitis.","authors":"Nitchanan Achararit, Phuntila Tharabenjasin, Prapasri Kulalert, Paskorn Sritipsukho, Sira Nanthapisal, Noel Pabalan, Nateetip Krishnamra, Panan Suntornsaratoon, Orapan Poachanukoon","doi":"10.12932/AP-241022-1486","DOIUrl":"10.12932/AP-241022-1486","url":null,"abstract":"<p><strong>Background: </strong>Zingiber cassumunar Roxb. (Phlai) has been used for the treatment of allergies including allergic rhinitis (AR). Although the anti-histamine effects have been reported, assessment of nasal cytokine and eosinophil production had not been investigated.</p><p><strong>Objective: </strong>This study aimed to examine the effect of Phlai on alterations in nasal pro-inflammatory cytokine levels and eosinophil counts in nasal mucosa.</p><p><strong>Methods: </strong>This was a randomized, double-blind, three-way crossover study. Nasal concentrations of cytokines, namely interleukin (IL)-4, IL-5, IL-13 and interferron-gamma (IFN-γ), nasal smear eosinophilia as well as total nasal symptom score (TNSS) were evaluated before and after a 4 weeks treatment with 200 mg Phlai capsules or placebo in 30 AR patients.</p><p><strong>Results: </strong>We observed significant (p < 0.05) reduction in IL-5, IL-13 as well as the number of eosinophils in subjects given Phlai. The degree of improvement of TNSS after Phlai treatment was initially manifested in week 2 with the greatest effect in week 4. In contrast, there were no significant differences in all nasal cytokines, eosinophil counts or TNSS between before and after receiving placebo.</p><p><strong>Conclusions: </strong>These findings provided the first evidence for the anti-allergic effect of Phlai which possibly involved inhibition of nasal pro-inflammatory cytokines production and eosinophilic recruitment. Phlai thus represents a promising herbal medicine for alleviating inflammation and AR symptoms.</p>","PeriodicalId":8552,"journal":{"name":"Asian Pacific journal of allergy and immunology","volume":" ","pages":"14-23"},"PeriodicalIF":5.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9886049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Notch signaling regulates function of human mucosal-associated invariant T (MAIT) cells. Notch信号调节人类粘膜相关不变T细胞(MAIT)的功能。
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-03-01 DOI: 10.12932/AP-010721-1174
Pimpayao Sodsai, Siriwan Klinchanhom, Nattiya Hirankarn, Rangsima Reantragoon, Tanapat Palaga

Background: Notch signaling plays an important role in the development of T lymphocytes and regulates their effector functions. The regulatory roles of Notch signaling on T cells have been intensely investigated, but whether it involves in effector functions of mucosal-associated invariant T (MAIT) cells has never been reported.

Objective: To elucidate the expression profiles of Notch receptors/ligands and to investigate their roles in human MAIT cell function.

Methods: Peripheral blood mononuclear cells (PBMCs) from health donors were stimulated with or without anti-CD3/ CD28-coupled beads, recombinant IL-12/IL-18 cytokines, riboflavin- or non-riboflavin-synthesizing bacterial cultured supernatant for 24 hours. The expression profiles of Notch receptors and ligands on MAIT cells were detected by flow cytometry. PBMCs were treated with a Notch signaling inhibitor, gamma secretase inhibitor (GSI), before stimulation to investigate the impact of interfering with Notch signaling on activation and function of MAIT cells.

Results: Resting MAIT cells predominantly expressed Notch2 receptor and the ligand, Jagged 2, on their surface. Upon stimulation, MAIT cells further upregulated Notch2 and also Notch1 with its cleaved form, indicating active Notch signaling. Cytokines and cytotoxic molecules which are secreted by activated MAIT cells, were suppressed by treatment with GSI. Moreover, both TCR-dependent MAIT cell activation by microbial-derived riboflavin intermediates and TCR-independent MAIT cell activation driven by IL-18 in synergy with IL-12, were blocked by GSI treatment.

Conclusions: Notch signaling is operating in MAIT cells and is involved in their activation both in a TCR-independent and -dependent manners.

背景:Notch信号在T淋巴细胞的发育过程中发挥着重要作用,并调节着T淋巴细胞的效应功能。Notch信号对T细胞的调控作用已被深入研究,但它是否参与粘膜相关不变T细胞(MAIT)的效应功能却从未有过报道:阐明Notch受体/配体的表达谱,并研究它们在人类MAIT细胞功能中的作用:方法:用或不用抗 CD3/ CD28 偶联珠、重组 IL-12/IL-18 细胞因子、核黄素或非核黄素合成细菌培养上清刺激健康供体的外周血单核细胞(PBMC)24 小时。流式细胞术检测了 MAIT 细胞上 Notch 受体和配体的表达谱。在刺激前用Notch信号抑制剂--γ分泌酶抑制剂(GSI)处理PBMC,以研究干扰Notch信号对MAIT细胞活化和功能的影响:静息的MAIT细胞表面主要表达Notch2受体和配体Jagged 2。刺激后,MAIT细胞进一步上调Notch2和Notch1及其裂解形式,表明Notch信号活跃。活化的 MAIT 细胞分泌的细胞因子和细胞毒性分子受到 GSI 的抑制。此外,GSI 还能阻断微生物衍生核黄素中间产物对 TCR 依赖性 MAIT 细胞活化,以及 IL-18 与 IL-12 协同作用驱动的 TCR 依赖性 MAIT 细胞活化:结论:Notch 信号在 MAIT 细胞中起作用,并以独立于 TCR 和独立于 TCR 的方式参与其活化。
{"title":"Notch signaling regulates function of human mucosal-associated invariant T (MAIT) cells.","authors":"Pimpayao Sodsai, Siriwan Klinchanhom, Nattiya Hirankarn, Rangsima Reantragoon, Tanapat Palaga","doi":"10.12932/AP-010721-1174","DOIUrl":"10.12932/AP-010721-1174","url":null,"abstract":"<p><strong>Background: </strong>Notch signaling plays an important role in the development of T lymphocytes and regulates their effector functions. The regulatory roles of Notch signaling on T cells have been intensely investigated, but whether it involves in effector functions of mucosal-associated invariant T (MAIT) cells has never been reported.</p><p><strong>Objective: </strong>To elucidate the expression profiles of Notch receptors/ligands and to investigate their roles in human MAIT cell function.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells (PBMCs) from health donors were stimulated with or without anti-CD3/ CD28-coupled beads, recombinant IL-12/IL-18 cytokines, riboflavin- or non-riboflavin-synthesizing bacterial cultured supernatant for 24 hours. The expression profiles of Notch receptors and ligands on MAIT cells were detected by flow cytometry. PBMCs were treated with a Notch signaling inhibitor, gamma secretase inhibitor (GSI), before stimulation to investigate the impact of interfering with Notch signaling on activation and function of MAIT cells.</p><p><strong>Results: </strong>Resting MAIT cells predominantly expressed Notch2 receptor and the ligand, Jagged 2, on their surface. Upon stimulation, MAIT cells further upregulated Notch2 and also Notch1 with its cleaved form, indicating active Notch signaling. Cytokines and cytotoxic molecules which are secreted by activated MAIT cells, were suppressed by treatment with GSI. Moreover, both TCR-dependent MAIT cell activation by microbial-derived riboflavin intermediates and TCR-independent MAIT cell activation driven by IL-18 in synergy with IL-12, were blocked by GSI treatment.</p><p><strong>Conclusions: </strong>Notch signaling is operating in MAIT cells and is involved in their activation both in a TCR-independent and -dependent manners.</p>","PeriodicalId":8552,"journal":{"name":"Asian Pacific journal of allergy and immunology","volume":" ","pages":"86-96"},"PeriodicalIF":5.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39664589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TGF-β1 induces epithelial-to-mesenchymal transition in chronic rhinosinusitis with nasal polyps through microRNA-182. TGF-β1通过microRNA-182诱导慢性鼻炎伴鼻息肉的上皮细胞向间质转化
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-03-01 DOI: 10.12932/AP-040921-1224
Wenxiu Jiang, Chun Zhou, Chengxin Ma, Yujie Cao, Guohong Hu, Huabin Li

Background: Epithelial-to-mesenchymal transition (EMT) in nasal epithelial cells is involved in tissue remodeling of chronic rhinosinusitis with nasal polyps (CRSwNP). Our study investigated the molecular mechanisms that microRNA-182 (miR-182) regulated EMT in eosinophilic (Eos) and non-eosinophilic (non-Eos) CRSwNP.

Objective: To investigate the mechanism by which miR-182 regulates EMT in human nasal epithelial cells (hNEPCs).

Methods: The expression of EMT markers (E-cadherin, N-cadherin and vimentin), transforming growth factor (TGF)-β1, and miR-182 were determined by western blotting and reverse transcription-quantitative PCR (RT-qPCR). Fluorescence in situ hybridization (FISH) was used to detect the miR-182 localization. Additionally, EMT markers expression and cell morphology changes were checked upon treatment with TGF-β1, or TGF-β1 with miR-182 inhibitor, or miR-182 mimics, or miR-182 inhibitor alone in hNEPCs.

Results: In both Eos CRSwNP and non-Eos CRSwNP, the expression levels of E-cadherin were downregulated while the expression levels of N-cadherin, vimentin, TGF-β1 and miR-182 were significantly upregulated compared with control nasal tissues. Additionally, more significant changes in these EMT markers were observed in the Eos-CRSwNP when compared with the non-Eos CRSwNP. Invitro hNEPCs model, TGF-β1 upregulated miR-182 expression and promoted EMT in hNEPCs, indicated by changes in cell morphology and EMT markers expression. Furthermore, these upregulations were reversed by miR-182 inhibitor.

Conclusions: This study showed that miR-182-induced EMT in response to TGF-β1 might promote nasal polypogenesis in both Eos CRSwNP and non-Eos CRSwNP, thus providing potential targets for the future development of novel therapeutic approaches for the management of CRSwNP.

背景:鼻上皮细胞的上皮-间质转化(EMT)参与了慢性鼻炎伴鼻息肉(CRSwNP)的组织重塑。我们的研究调查了microRNA-182(miR-182)调控嗜酸性(Eos)和非嗜酸性(non-Eos)CRSwNP中EMT的分子机制:研究 miR-182 调节人鼻腔上皮细胞(hNEPCs)EMT 的机制:方法:采用Western印迹法和逆转录定量PCR(RT-qPCR)法测定EMT标记物(E-cadherin、N-cadherin和vimentin)、转化生长因子(TGF)-β1和miR-182的表达。荧光原位杂交(FISH)用于检测 miR-182 的定位。此外,在使用 TGF-β1、TGF-β1 与 miR-182 抑制剂、miR-182 模拟物或单独使用 miR-182 抑制剂处理 hNEPCs 时,检测了 EMT 标记物的表达和细胞形态的变化:结果:与对照鼻组织相比,Eos CRSwNP和非Eos CRSwNP中E-cadherin的表达水平均下调,而N-cadherin、vimentin、TGF-β1和miR-182的表达水平均显著上调。此外,与非 Eos CRSwNP 相比,在 Eos-CRSwNP 中观察到这些 EMT 标记发生了更明显的变化。在诱导 hNEPCs 模型中,TGF-β1 上调了 miR-182 的表达并促进了 hNEPCs 的 EMT,这表现在细胞形态和 EMT 标记表达的变化上。此外,这些上调被miR-182抑制剂逆转:本研究表明,miR-182 对 TGF-β1 诱导的 EMT 可促进 Eos CRSwNP 和非 Eos CRSwNP 的鼻息肉发生,从而为未来开发治疗 CRSwNP 的新型疗法提供了潜在靶点。
{"title":"TGF-β1 induces epithelial-to-mesenchymal transition in chronic rhinosinusitis with nasal polyps through microRNA-182.","authors":"Wenxiu Jiang, Chun Zhou, Chengxin Ma, Yujie Cao, Guohong Hu, Huabin Li","doi":"10.12932/AP-040921-1224","DOIUrl":"10.12932/AP-040921-1224","url":null,"abstract":"<p><strong>Background: </strong>Epithelial-to-mesenchymal transition (EMT) in nasal epithelial cells is involved in tissue remodeling of chronic rhinosinusitis with nasal polyps (CRSwNP). Our study investigated the molecular mechanisms that microRNA-182 (miR-182) regulated EMT in eosinophilic (Eos) and non-eosinophilic (non-Eos) CRSwNP.</p><p><strong>Objective: </strong>To investigate the mechanism by which miR-182 regulates EMT in human nasal epithelial cells (hNEPCs).</p><p><strong>Methods: </strong>The expression of EMT markers (E-cadherin, N-cadherin and vimentin), transforming growth factor (TGF)-β1, and miR-182 were determined by western blotting and reverse transcription-quantitative PCR (RT-qPCR). Fluorescence in situ hybridization (FISH) was used to detect the miR-182 localization. Additionally, EMT markers expression and cell morphology changes were checked upon treatment with TGF-β1, or TGF-β1 with miR-182 inhibitor, or miR-182 mimics, or miR-182 inhibitor alone in hNEPCs.</p><p><strong>Results: </strong>In both Eos CRSwNP and non-Eos CRSwNP, the expression levels of E-cadherin were downregulated while the expression levels of N-cadherin, vimentin, TGF-β1 and miR-182 were significantly upregulated compared with control nasal tissues. Additionally, more significant changes in these EMT markers were observed in the Eos-CRSwNP when compared with the non-Eos CRSwNP. Invitro hNEPCs model, TGF-β1 upregulated miR-182 expression and promoted EMT in hNEPCs, indicated by changes in cell morphology and EMT markers expression. Furthermore, these upregulations were reversed by miR-182 inhibitor.</p><p><strong>Conclusions: </strong>This study showed that miR-182-induced EMT in response to TGF-β1 might promote nasal polypogenesis in both Eos CRSwNP and non-Eos CRSwNP, thus providing potential targets for the future development of novel therapeutic approaches for the management of CRSwNP.</p>","PeriodicalId":8552,"journal":{"name":"Asian Pacific journal of allergy and immunology","volume":" ","pages":"61-73"},"PeriodicalIF":5.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39763036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differences in asthma-related outcomes by anti-IL-5 biologics, omalizumab, and dupilumab based on blood eosinophil counts. 基于血液嗜酸性粒细胞计数的抗IL-5生物制剂、奥马珠单抗和杜比鲁单抗对哮喘相关结果的影响差异。
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-01-06 DOI: 10.12932/AP-290623-1645
Yuya Kimura, Maho Suzukawa, Norihiko Inoue, Shinobu Imai, Hiromasa Horiguchi, Manabu Akazawa, Hirotoshi Matsui

Background: Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made.

Objective: To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab in reducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups.

Methods: A retrospective cohort study using the National Hospital Organization database (2016-2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model.

Results: Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34-1.08); dupilumab vs. anti-IL-5: 1.48 (0.81-2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83-1.54); dupilumab vs. anti-IL-5: 2.69 (1.91-3.78)] in these respective groups. In patients with eosinophil of ≥ 300/μL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82-4.46)]. In patients with eosinophil of < 300/μL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13-0.51)].

Conclusion: Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil counts, while less effective than omalizumab in patients with low eosinophil counts.

背景:根据 2 型生物标志物选择最佳生物制剂一直是重症哮喘治疗领域的关注点。然而,基于生物标志物分层的直接比较还很少:比较抗IL-5(mepolizumab、benralizumab)、奥马珠单抗和杜匹单抗在减少所有亚组和嗜酸性粒细胞分层亚组的哮喘住院次数和病情加重次数方面的有效性:利用国家医院组织数据库(2016-2020年)进行了一项回顾性队列研究。研究选择了使用生物制剂的哮喘患者,并使用反概率治疗加权倾向评分平衡了各组的基线背景。采用泊松回归模型得出加权比率(RR):在使用生物制剂的 320 名哮喘患者中,205 人(64.1%)、75 人(23.4%)和 40 人(12.5%)分别被归入抗 IL-5、奥马珠单抗和杜匹单抗组。加权后,每 100 人年分别有 47.1 人、30.0 人和 62.6 人住院[奥马珠单抗 vs. 抗 IL-5:加权 RR,0.61(0.34-1.08);杜匹单抗 vs. 抗 IL-5:1.48(0.81-2.72)],以及每百人年分别出现 117.0、134.6 和 287.3 次病情加重[奥马珠单抗 vs. 抗-IL-5:1.13(0.83-1.54);杜匹单抗 vs. 抗-IL-5:2.69(1.91-3.78)]。在嗜酸性粒细胞≥300/μL的患者中,与抗IL-5组相比,dupilumab组的病情加重率更高[加权RR,2.85(1.82-4.46)]。在嗜酸性粒细胞小于300/μL的患者中,奥马珠单抗组的住院率低于抗IL-5组[加权RR,0.32(0.13-0.51)]:抗IL-5生物制剂对嗜酸性粒细胞计数高的患者可能比杜匹单抗更有效,而对嗜酸性粒细胞计数低的患者则不如奥马珠单抗有效。
{"title":"Differences in asthma-related outcomes by anti-IL-5 biologics, omalizumab, and dupilumab based on blood eosinophil counts.","authors":"Yuya Kimura, Maho Suzukawa, Norihiko Inoue, Shinobu Imai, Hiromasa Horiguchi, Manabu Akazawa, Hirotoshi Matsui","doi":"10.12932/AP-290623-1645","DOIUrl":"https://doi.org/10.12932/AP-290623-1645","url":null,"abstract":"<p><strong>Background: </strong>Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made.</p><p><strong>Objective: </strong>To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab in reducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups.</p><p><strong>Methods: </strong>A retrospective cohort study using the National Hospital Organization database (2016-2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model.</p><p><strong>Results: </strong>Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34-1.08); dupilumab vs. anti-IL-5: 1.48 (0.81-2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83-1.54); dupilumab vs. anti-IL-5: 2.69 (1.91-3.78)] in these respective groups. In patients with eosinophil of ≥ 300/μL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82-4.46)]. In patients with eosinophil of < 300/μL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13-0.51)].</p><p><strong>Conclusion: </strong>Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil counts, while less effective than omalizumab in patients with low eosinophil counts.</p>","PeriodicalId":8552,"journal":{"name":"Asian Pacific journal of allergy and immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anaphylaxis in children: Effect of age and atopic status. 儿童过敏性休克:年龄和特应性状态的影响。
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-01-06 DOI: 10.12932/AP-310723-1664
Nutthakit Wong-Onta, Adithep Sawatchai, Watcharoot Kanchongkittiphon, Wiparat Manuyakorn

Background: Anaphylaxis is a life-threatening allergic reaction with rising incidence worldwide. Young children's limited ability to express symptoms adds unique diagnostic challenges.

Objective: To study on anaphylaxis in children, including triggers, symptoms, treatment, atopic status impact, and adrenaline injection time intervals.

Methods: In-patient medical records of children who were diagnosed with anaphylaxis during 2014-2021 were reviewed.

Results: One hundred thirty-three anaphylaxis events were identified. Food (47%) was the most common trigger, followed by drugs (31%), blood components (17%), insects (3%), and idiopathic causes (2%). Ten cases of refractory anaphylaxis, 2 cases of biphasic reactions, and 1 case of persistent anaphylaxis were found. There were no reported fatalities. The most common presentations involved the skin (94%), followed by the respiratory (73%), gastrointestinal (47%), and cardiovascular (42%) systems. In atopic patients, wheezing was more prominent than in those without atopy (p-value = 0.017). In the non-atopic patients, there was a higher incidence of cardiovascular symptoms, particularly hypotension (p-value = 0.001), compared to individuals with atopy. Children under 5 years old with mild-moderate anaphylaxis required more time to reach the hospital (147.0 vs. 45.0 minutes, p = 0.033) and to receive adrenaline injections (35.0 vs. 9.0 minutes, p-value = 0.017) than those with severe anaphylaxis.

Conclusion: Childhood anaphylaxis is prevalent. Children with mild-moderate anaphylaxis experienced delays in hospital visits and adrenaline administration. Education on allergies is needed to improve the identification and prompt response to anaphylactic reactions, especially in young children.

背景:过敏性休克是一种危及生命的过敏反应,在全球的发病率不断上升。幼儿表达症状的能力有限,这给诊断带来了独特的挑战:研究儿童过敏性休克,包括诱因、症状、治疗、特应性状态影响和肾上腺素注射时间间隔:方法:查阅 2014-2021 年间被诊断为过敏性休克的儿童住院病历:结果:共发现 133 起过敏性休克事件。食物(47%)是最常见的诱发因素,其次是药物(31%)、血液成分(17%)、昆虫(3%)和特发性原因(2%)。共发现 10 例难治性过敏性休克、2 例双相反应和 1 例持续性过敏性休克。没有死亡病例的报告。最常见的症状涉及皮肤系统(94%),其次是呼吸系统(73%)、胃肠道系统(47%)和心血管系统(42%)。在特应性患者中,喘息比非特应性患者更明显(P 值 = 0.017)。与特应病患者相比,非特应病患者出现心血管症状,尤其是低血压(p 值 = 0.001)的几率更高。与重度过敏性休克患者相比,患有轻度-中度过敏性休克的 5 岁以下儿童需要更多时间到达医院(147.0 分钟对 45.0 分钟,p = 0.033)和接受肾上腺素注射(35.0 分钟对 9.0 分钟,p 值 = 0.017):结论:儿童过敏性休克很普遍。结论:过敏性休克在儿童中普遍存在,轻度至中度过敏性休克的儿童在医院就诊和肾上腺素注射方面都会出现延误。需要开展过敏教育,以提高过敏反应的识别能力和及时应对能力,尤其是在幼儿中。
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引用次数: 0
Serum levels of specific IgE to cow's milk and its components as predictors of anaphylaxis in Chinese children with cow's milk allergy. 预测中国牛奶过敏儿童过敏性休克的牛奶及其成分特异性 IgE 血清水平。
IF 5 4区 医学 Q3 ALLERGY Pub Date : 2024-01-06 DOI: 10.12932/AP-010823-1667
Wanting Qi, Jialing Chen, Huishuang Zheng, Wenjing Zhu, Kai Guan, Li Sha

Background: Cow's milk allergy (CMA) is one of the most common food allergies in young children. As improved diagnostic tools, allergic tests are inconsistent and limited in predicting anaphylaxis.

Objective: To explore risk factors for anaphylaxis and to determine practical cut-offs for allergic tests in predicting anaphylaxis.

Methods: This is a prospective cohort study. Children with IgE-mediated CMA were enrolled and divided into three groups (Group 1: non-anaphylaxis; Group 2: GRADE I anaphylaxis; Group 3: GRADE II-IV anaphylaxis that warranted epinephrine). Prick-to-prick tests (PTPs) using fresh cow's milk (CM) were performed. Serum specific IgE (sIgE) against CM and its components, including casein, alpha-lactalbumin, beta-lactoglobulin, and bovine serum albumin were measured. The 90% and 95% positive predictive value (PPV) decision points for predicting anaphylaxis were determined. Potential predictors of anaphylaxis were evaluated in logistic regression models.

Results: This study included 134 CMA patients with a median age of 14.4 months. The sensitization rate to any CM component was 89%. Group 3 was more likely to be sensitized to multiple CM components and have higher sIgE levels. The 95% PPV diagnostic decision points of casein-sIgE in predicting anaphylaxis was 13.0 kUA/L. For GRADE II-IV anaphylaxis, casein-sIgE ≥ 54.9 kUA/L could provide a PPV of 88.9%. The elevated casein-sIgE level (OR 14.0, P=0.025) and complicating respiratory allergic diseases (OR 4.8, P=0.022) were independent risk factors for GRADE II-IV anaphylaxis.

Conclusion: High casein-sIgE levels are strongly associated with CM anaphylaxis. Detection of casein-sIgE may offer an additional value for the prediction of CM anaphylaxis.

背景:牛奶过敏(CMA)是幼儿最常见的食物过敏之一。作为改良的诊断工具,过敏试验在预测过敏性休克方面存在不一致和局限性:目的:探讨过敏性休克的风险因素,并确定过敏试验在预测过敏性休克方面的实用临界值:这是一项前瞻性队列研究。方法:这是一项前瞻性队列研究。研究人员招募了 IgE 介导的 CMA 患儿,并将其分为三组(第 1 组:非过敏性休克;第 2 组:GRADE I 型过敏性休克;第 3 组:GRADE II-IV 型过敏性休克,需要使用肾上腺素)。使用新鲜牛乳(CM)进行针刺试验(PTP)。测定了针对 CM 及其成分(包括酪蛋白、α-乳白蛋白、β-乳球蛋白和牛血清白蛋白)的血清特异性 IgE(sIgE)。确定了预测过敏性休克的 90% 和 95% 阳性预测值 (PPV) 决策点。在逻辑回归模型中对过敏性休克的潜在预测因素进行了评估:本研究共纳入 134 名 CMA 患者,中位年龄为 14.4 个月。对任何中药成分过敏的比例为 89%。第 3 组更有可能对多种中药成分过敏,且 sIgE 水平更高。酪蛋白-sIgE 预测过敏性休克的 95% PPV 诊断决策点为 13.0 kUA/L。对于 GRADE II-IV 级过敏性休克,酪蛋白-SIgE ≥ 54.9 kUA/L 可提供 88.9% 的 PPV。酪蛋白-SIgE水平升高(OR 14.0,P=0.025)和并发呼吸道过敏性疾病(OR 4.8,P=0.022)是GRADE II-IV过敏性休克的独立危险因素:结论:高酪蛋白-SIgE水平与CM过敏性休克密切相关。结论:高酪蛋白-SIgE水平与CM过敏性休克密切相关,酪蛋白-SIgE的检测可为CM过敏性休克的预测提供额外价值。
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引用次数: 0
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Asian Pacific journal of allergy and immunology
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