Clinical immunology最新文献_第7页

Cladribine tablets in relapsing-remitting multiple sclerosis preferentially target B-cells 治疗复发缓解型多发性硬化症的克拉利宾片优先靶向 B 细胞。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-10-18 DOI: 10.1016/j.clim.2024.110380

Francesca Ammoscato , Mohammad Wafa , Justyna Skonieczna , Jonathan Bestwick , Rosemary Monero , Michael Andrews , Stefania De Trane , David Holden , Ashok Adams , Lucia Bianchi , Ben Turner , Monica Marta , Klaus Schmierer , David Baker , Gavin Giovannoni , Sharmilee Gnanapavan

{"title":"Cladribine tablets in relapsing-remitting multiple sclerosis preferentially target B-cells","authors":"Francesca Ammoscato , Mohammad Wafa , Justyna Skonieczna , Jonathan Bestwick , Rosemary Monero , Michael Andrews , Stefania De Trane , David Holden , Ashok Adams , Lucia Bianchi , Ben Turner , Monica Marta , Klaus Schmierer , David Baker , Gavin Giovannoni , Sharmilee Gnanapavan","doi":"10.1016/j.clim.2024.110380","DOIUrl":"10.1016/j.clim.2024.110380","url":null,"abstract":"<div><div>Recent studies demonstrate the efficacy of B cell-targeting therapies in managing multiple sclerosis (MS) activity, emphasizing the critical role of B cells in MS pathogenesis. CladB study aimed to quantify the temporal changes in peripheral immune cells and their activity over 96 weeks of Cladribine tablets (CladT) treatment in relapsing-remitting MS (RRMS).</div><div>Ten participants (3 males, 7 females) had blood samples collected at multiple intervals (Day 0, 1, 5, then weekly for 8 weeks, biweekly for up to 24 weeks, and monthly for up to 96 weeks) for immune cell analysis, compared to a historical alemtuzumab-treated cohort. Paired cerebrospinal fluid (CSF) was also taken for various analyses, alongside clinical and brain imaging assessments.</div><div>CladT depleted memory B cells, while alemtuzumab rapidly depleted T and B cells. The кFLC index decreased from 164.5 ± 227.1 to 71.3 ± 84.7 at 48 weeks (<em>p</em> = 0.002) and to 64.4 ± 67.3 at 96 weeks (<em>p</em> = 0.01). The IgG index dropped from 1.1 ± 0.5 at baseline to 0.8 ± 0.4 at 48 weeks (<em>p</em> = 0.014) and to 0.8 ± 0.3 at 96 weeks (<em>p</em> = 0.02). CSF CXCL-13 decreased from 88.6 ± 68.4 pg/mL to 39.4 ± 35.2 pg/mL at 48 weeks (<em>p</em> = 0.037) and 19.1 ± 11.7 pg/mL at 96 weeks (<em>p</em> = 0.027). CSF NfL levels were reduced at 48 weeks (<em>p</em> = 0.01).</div><div>CladT primarily depletes memory B cells and antibody-secreting cell precursors in RRMS, leading to sustained effects on intrathecal antibody production and total IgG, and a reduction in CSF CXCL-13.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110380"},"PeriodicalIF":4.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Successful treatment with tofacitinib in a child diagnosed with ISG15 deficiency 用托法替尼成功治疗了一名被诊断为 ISG15 缺乏症的儿童。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-10-12 DOI: 10.1016/j.clim.2024.110377

Sara Murias Loza , Virginia Courel Del Río , Estefanía Pardo Campo , Laura Calle-Miguel , Gonzalo Anes González , Julián Rodríguez Suárez

引用次数: 0

Dysregulation of neutrophil extracellular traps (NETs)-related genes in the pathogenesis of diabetic kidney disease - Results from bioinformatics analysis and translational studies 中性粒细胞胞外捕获物（NET）相关基因在糖尿病肾病发病机制中的失调--生物信息学分析和转化研究的结果

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-10-11 DOI: 10.1016/j.clim.2024.110379

Ruiyan Xie , Ka Ho Jason Sher , Sin Yu Cindy Tang , Irene Ya Lin Yam , C.H. Lee , Qiongli Wu , Desmond Yat Hin Yap

{"title":"Dysregulation of neutrophil extracellular traps (NETs)-related genes in the pathogenesis of diabetic kidney disease - Results from bioinformatics analysis and translational studies","authors":"Ruiyan Xie , Ka Ho Jason Sher , Sin Yu Cindy Tang , Irene Ya Lin Yam , C.H. Lee , Qiongli Wu , Desmond Yat Hin Yap","doi":"10.1016/j.clim.2024.110379","DOIUrl":"10.1016/j.clim.2024.110379","url":null,"abstract":"<div><div>The role of Neutrophil extracellular traps (NETs) in the immunopathogenesis of Diabetic Kidney Disease (DKD) remains elusive. We used a machine learning approach to identify differentially expressed genes (DEGs) associated with NETs in human DKD kidney biopsy datasets and validated the results using single-nucleus RNA sequencing datasets. The expressions of these candidate genes and related cytokines were verified in blood obtained from DKD patients. Three NETs-associated genes (ITGAM, ITGB2 and TLR7) were identified, which all showed significant upregulation in both glomerular and tubulointerstitial compartments in human DKD kidneys. DKD patients showed significantly higher number of activated neutrophils with increased ITGAM and ITGB2 expression, higher serum IL-6 but lower IL-10, compared to healthy controls (p all <0.01). This study suggests that dysregulation of NETs-associated genes ITGAM and ITGB2 are related to the pathogenesis of DKD, and may serve as novel diagnostic markers and therapeutic targets in DKD.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110379"},"PeriodicalIF":4.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Phenotypic, transcriptomic, and spatial characterization of CD45RB+ naïve mature B cells: Implications in Sjögren's disease CD45RB+幼稚成熟B细胞的表型、转录组和空间特征：对斯约格伦病的影响。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-10-10 DOI: 10.1016/j.clim.2024.110378

Marina Boudigou , Marie Frutoso , Patrice Hémon , Christelle Le Dantec , Loukas Chatzis , Valérie Devauchelle , Christophe Jamin , Divi Cornec , Jacques-Olivier Pers , Laëtitia Le Pottier , Sophie Hillion

引用次数: 0

Neudesin regulates dendritic cell function and antitumor CD8+ T cell immunity Neudesin 可调节树突状细胞功能和抗肿瘤 CD8+ T 细胞免疫。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-10-05 DOI: 10.1016/j.clim.2024.110376

Yuki Masuda, Naoto Kondo, Yoshiaki Nakayama, Ryohei Shimizu, Morichika Konishi

引用次数: 0

Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis 先天性免疫错误患者的临床外显子组测序数据：队列水平的诊断率和系统性再分析的益处。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-10-05 DOI: 10.1016/j.clim.2024.110375

Emil E. Vorsteveld , Caspar I. Van der Made , Sanne P. Smeekens , Janneke H. Schuurs-Hoeijmakers , Galuh Astuti , Heleen Diepstra , Christian Gilissen , Evelien Hoenselaar , Alice Janssen , Kees van Roozendaal , Jettie Sikkema-van Engelen , Wouter Steyaert , Marjan M. Weiss , Helger G. Yntema , Tuomo Mantere , Mofareh S. AlZahrani , Koen van Aerde , Beata Derfalvi , Eissa Ali Faqeih , Stefanie S.V. Henriet , Alexander Hoischen

{"title":"Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis","authors":"Emil E. Vorsteveld , Caspar I. Van der Made , Sanne P. Smeekens , Janneke H. Schuurs-Hoeijmakers , Galuh Astuti , Heleen Diepstra , Christian Gilissen , Evelien Hoenselaar , Alice Janssen , Kees van Roozendaal , Jettie Sikkema-van Engelen , Wouter Steyaert , Marjan M. Weiss , Helger G. Yntema , Tuomo Mantere , Mofareh S. AlZahrani , Koen van Aerde , Beata Derfalvi , Eissa Ali Faqeih , Stefanie S.V. Henriet , Alexander Hoischen","doi":"10.1016/j.clim.2024.110375","DOIUrl":"10.1016/j.clim.2024.110375","url":null,"abstract":"<div><div>While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated <em>in silico</em> IEI gene panel. Variants were classified and curated through expert review. The molecular diagnostic yield after standard exome analysis was 11.8 %. Through systematic reanalysis, we identified variants of interest in 5.2 % of undiagnosed patients, with 76.7 % being (candidate) disease-causing, providing a (candidate) diagnosis in 15.2 % of our cohort. We find a 1.7 percentage point increase in conclusive molecular diagnoses. We find a high degree of actionability in patients with a genetic diagnosis (76.4 %). Despite the modest absolute diagnostic gain, these data support the benefit of iterative exome reanalysis in IEI patients, conveying the notion that our current understanding of genes and variants involved in IEI is by far not saturated.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110375"},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective immunity to repeated COVID-19 breakthrough infections 对 COVID-19 反复突破性感染的保护性免疫。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-09-30 DOI: 10.1016/j.clim.2024.110374

Daniel M. Altmann , Rosemary J. Boyton

引用次数: 0

Anti-interferon gamma-inducible protein 16 antibodies: Identification of a novel autoantigen in idiopathic interstitial pneumonia and its clinical characteristics based on a multicenter cohort study 抗干扰素γ诱导蛋白16抗体：基于多中心队列研究的特发性间质性肺炎新型自身抗原鉴定及其临床特征。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-09-30 DOI: 10.1016/j.clim.2024.110372

Tsuneo Sasai , Ran Nakashima , Tomohiro Handa , Yasuhiko Yamano , Yasuhiro Kondo , Shogo Matsuda , Takuya Kotani , Hiromi Tomioka , Ryo Tachikawa , Keisuke Tomii , Kiminobu Tanizawa , Yasuhiro Nohda , Toshiaki Kogame , Mirei Shirakashi , Ryosuke Hiwa , Hideaki Tsuji , Shuji Akizuki , Hajime Yoshifuji , Tsuneyo Mimori , Kenji Kabashima , Akio Morinobu

{"title":"Anti-interferon gamma-inducible protein 16 antibodies: Identification of a novel autoantigen in idiopathic interstitial pneumonia and its clinical characteristics based on a multicenter cohort study","authors":"Tsuneo Sasai , Ran Nakashima , Tomohiro Handa , Yasuhiko Yamano , Yasuhiro Kondo , Shogo Matsuda , Takuya Kotani , Hiromi Tomioka , Ryo Tachikawa , Keisuke Tomii , Kiminobu Tanizawa , Yasuhiro Nohda , Toshiaki Kogame , Mirei Shirakashi , Ryosuke Hiwa , Hideaki Tsuji , Shuji Akizuki , Hajime Yoshifuji , Tsuneyo Mimori , Kenji Kabashima , Akio Morinobu","doi":"10.1016/j.clim.2024.110372","DOIUrl":"10.1016/j.clim.2024.110372","url":null,"abstract":"<div><div>Autoantibodies are detected in idiopathic interstitial pneumonias (IIPs) without a clear connective tissue disease diagnosis, and their clinical significance is unclear. This study aimed to identify a novel autoantibody in IIPs. We screened 295 IIP patients using a <sup>35</sup>S-methionine labeled protein immunoprecipitation assay. Candidate autoantigens were identified via protein array and confirmed by immunoprecipitation. Six sera from 295 IIP patients immunoprecipitated common tetrameric proteins (100 kDa). The protein array identified interferon gamma-inducible protein 16 (IFI16) as the candidate autoantigen. Patients with anti-IFI16 antibodies received immunosuppressants less frequently. Five-year survival rates were 50 %, 69 %, and 63 % (<em>P</em> = 0.60), and acute exacerbation-free rates were 50 %, 96 %, and 84 % (<em>P</em> = 0.15) for patients with anti-IFI16, anti-aminoacyl tRNA antibodies, and others. Anti-IFI16 is a novel autoantibody in IIPs. Patients with this antibody often receive less immunosuppressive therapy and could have a poor prognosis. Further research is needed to refine patient stratification and management.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110372"},"PeriodicalIF":4.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Broad applicability of the Goldspire™ platform for the treatment of solid tumors Goldspire™ 平台广泛适用于实体瘤的治疗。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-09-28 DOI: 10.1016/j.clim.2024.110373

Jenny Zilberberg , Christopher Uhl , Charles B. Scott , David W. Andrews , Mark A. Exley

{"title":"Broad applicability of the Goldspire™ platform for the treatment of solid tumors","authors":"Jenny Zilberberg , Christopher Uhl , Charles B. Scott , David W. Andrews , Mark A. Exley","doi":"10.1016/j.clim.2024.110373","DOIUrl":"10.1016/j.clim.2024.110373","url":null,"abstract":"<div><div>Goldspire™ is a personalized immunotherapy platform that combines whole tumor-derived cells with antisense oligonucleotide (IMV-001) against Insulin-Like Growth Factor-1 Receptor (IGF-1R) in biodiffusion chambers (BDCs; 0.1 μm pore). BDCs are exposed to 5–6 Gy and implanted at abdominal sites for ∼48 h to deliver an antigenic payload and immunostimulatory factors to train the immune system. Lead product IGV-001 was evaluated in newly diagnosed glioblastoma (ndGBM) patients in Phase 1a and 1b trials (<span><span>NCT02507583</span><svg><path></path></svg></span>). A Phase 2b study (<span><span>NCT04485949</span><svg><path></path></svg></span>) recently completed enrollment.</div><div>Preventative treatment with tumor-specific products manufactured with Goldspire limited tumor progression and extended overall survival in mice challenged with bladder, pancreatic, ovarian, colorectal, or renal carcinomas. The benefit of this immunotherapy was enhanced with anti-PD-1; combination treatment was superior to either monotherapy in orthotopic GBM and melanoma models. Lastly, Goldspire elicited immune T cell activation and memory phenotypes against patient-derived endometrial tumor-derived products in co-cultures with matching immune cells.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110373"},"PeriodicalIF":4.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bisphenol A triggers activation of ocular immune system and aggravates allergic airway inflammation 双酚 A 会引发眼部免疫系统激活，加重过敏性气道炎症。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-09-28 DOI: 10.1016/j.clim.2024.110370

Tatsuo Ueda , Takumi Adachi , Tomoya Hayashi , Koubun Yasuda , Kazufumi Matsushita , Eiko Koike , Rie Yanagisawa , Takahiro Nagatake , Jun Kunisawa , Ken J. Ishii , Kenzo Tsuzuki , Etsushi Kuroda

{"title":"Bisphenol A triggers activation of ocular immune system and aggravates allergic airway inflammation","authors":"Tatsuo Ueda , Takumi Adachi , Tomoya Hayashi , Koubun Yasuda , Kazufumi Matsushita , Eiko Koike , Rie Yanagisawa , Takahiro Nagatake , Jun Kunisawa , Ken J. Ishii , Kenzo Tsuzuki , Etsushi Kuroda","doi":"10.1016/j.clim.2024.110370","DOIUrl":"10.1016/j.clim.2024.110370","url":null,"abstract":"<div><div>Bisphenol A (BPA) is widely used in manufacturing plastic products, and it has been reported that exposure through the airway or orally aggravates allergic airway inflammation. Because BPA is detected in the atmosphere and indoor environments, the eyes can also be exposed to BPA. After ocular exposure to BPA and antigen via eye drops, we observed enhanced antigen uptake of antigen-presenting cells (APCs) in tear duct-associated lymphoid tissue (TALT). Additionally, we observed the formation of germinal center (GC) B cells in TALT and induction of allergic airway inflammation in mice sensitized with BPA and antigen via eye drops, followed by airway antigen exposure. We also found that DNAX-activating protein of 12 kDa (DAP12)-deficient mice displayed impaired activation of APCs enhanced by ocular exposure to BPA. These results indicate that ocular sensitization to BPA and allergen triggers allergic inflammation via TALT activation, and that DAP12 might be a key molecule for modulating the ocular immune system.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110370"},"PeriodicalIF":4.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0