Clinical immunology最新文献_第10页

Expansion of tumor-infiltrating lymphocytes in non-small cell lung cancer: Clinical potential and efficacy in EGFR mutation subsets 非小细胞肺癌中肿瘤浸润淋巴细胞的扩增：表皮生长因子受体突变亚群的临床潜力和疗效。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-06-20 DOI: 10.1016/j.clim.2024.110289

Hyun Lee , Miseon Lee , Chae Lyul Lim , Hye Seon Park , In Hye Song , Byung-Kwan Jeong , Dong Kwan Kim , Yong-Hee Kim , Sehoon Choi , Geun Dong Lee , Sae Byul Lee , SungWook Jung , Gyungyub Gong , Sung-Bae Kim , Changhoon Yoo , Joo Young Kim , Hee Jin Lee

{"title":"Expansion of tumor-infiltrating lymphocytes in non-small cell lung cancer: Clinical potential and efficacy in EGFR mutation subsets","authors":"Hyun Lee , Miseon Lee , Chae Lyul Lim , Hye Seon Park , In Hye Song , Byung-Kwan Jeong , Dong Kwan Kim , Yong-Hee Kim , Sehoon Choi , Geun Dong Lee , Sae Byul Lee , SungWook Jung , Gyungyub Gong , Sung-Bae Kim , Changhoon Yoo , Joo Young Kim , Hee Jin Lee","doi":"10.1016/j.clim.2024.110289","DOIUrl":"10.1016/j.clim.2024.110289","url":null,"abstract":"<div><p>Our study aimed to expand tumor-infiltrating lymphocytes (TILs) from primary non-small cell lung cancers (NSCLCs) and evaluate their reactivity against tumor cells. We expanded TILs from 103 primary NSCLCs using histopathological analysis, flow cytometry, IFN-γ release assays, cell-mediated cytotoxicity assays, and <em>in vivo</em> efficacy tests. TIL expansion was observed in all cases, regardless of <em>EGFR</em> mutation status. There was also an increase in the median CD4<sup>+</sup>/CD8<sup>+</sup> ratio during expansion. In post-rapid expansion protocol (REP) TILs, 13 out of 16 cases, including all three cases with <em>EGFR</em> mutations, exhibited a two-fold or greater increase in IFN-γ secretion. The cytotoxicity assay revealed enhanced tumor cell death in three of the seven cases, two of which had <em>EGFR</em> mutations. <em>In vivo</em> functional testing in a patient-derived xenograft model showed a reduction in tumor volume. The anti-tumor activity of post-REP TILs underscores their potential as a therapeutic option for advanced NSCLC, irrespective of mutation status.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110289"},"PeriodicalIF":4.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440264","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

The ‘T' (Tsokos) cells: Celebrating Dr. George Tsokos' pioneering contributions to clinical immunology T"（佐科斯）细胞：纪念乔治-佐科斯博士对临床免疫学的开创性贡献。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-06-20 DOI: 10.1016/j.clim.2024.110286

引用次数: 0

A tale of two functions: C-reactive protein complement-ary structures and their role in rheumatoid arthritis 两种功能的故事：C 反应蛋白的补体结构及其在类风湿性关节炎中的作用

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-06-15 DOI: 10.1016/j.clim.2024.110281

Coziana Ciurtin , Ghada Adly Helmy , Alexia Correia Ferreira , Jessica J. Manson , Elizabeth C. Jury , Thomas McDonnell

{"title":"A tale of two functions: C-reactive protein complement-ary structures and their role in rheumatoid arthritis","authors":"Coziana Ciurtin , Ghada Adly Helmy , Alexia Correia Ferreira , Jessica J. Manson , Elizabeth C. Jury , Thomas McDonnell","doi":"10.1016/j.clim.2024.110281","DOIUrl":"10.1016/j.clim.2024.110281","url":null,"abstract":"<div><p>C-reactive protein (CRP) is an inflammatory biomarker with associated clinical utility in a wide number of inflammatory disorders, including rheumatoid arthritis (RA). The interaction of CRP with pro-inflammatory cytokines has been explored before, however its role in complement regulation is more subtle, where CRP is capable of both up and downregulating the complement cascade. CRP is produced in a pentameric form and can dissociate to a monomeric form in circulation which has significant implications for its ability to interact with receptors and binding partners. This dichotomy of CRP structure could have relevance in patients with RA who have significant dysfunction in their complement cascade and also widely varying CRP levels including at the time of flare. This review aims to bring together current knowledge of CRP in its various forms, its effects on complement function and how this could influence pathology in the context of RA.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110281"},"PeriodicalIF":4.5,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003905/pdfft?md5=397fe8084f3264b5b0b1b47588435ea0&pid=1-s2.0-S1521661624003905-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141398017","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

Tissue gene expression profiles and communication networks inform candidate blood biomarker identification in psoriasis and atopic dermatitis 组织基因表达谱和通讯网络为牛皮癣和特应性皮炎候选血液生物标记物的鉴定提供信息。

IF 8.6 3区医学

Clinical immunology Pub Date : 2024-06-15 DOI: 10.1016/j.clim.2024.110283

J. Soul , E. Carlsson , S.R. Hofmann , S. Russ , J. Hawkes , F. Schulze , M. Sergon , J. Pablik , S. Abraham , C.M. Hedrich

{"title":"Tissue gene expression profiles and communication networks inform candidate blood biomarker identification in psoriasis and atopic dermatitis","authors":"J. Soul , E. Carlsson , S.R. Hofmann , S. Russ , J. Hawkes , F. Schulze , M. Sergon , J. Pablik , S. Abraham , C.M. Hedrich","doi":"10.1016/j.clim.2024.110283","DOIUrl":"10.1016/j.clim.2024.110283","url":null,"abstract":"<div><p>Overlapping clinical and pathomechanistic features can complicate the diagnosis and treatment of inflammatory skin diseases, including psoriasis and atopic dermatitis (AD). Spatial transcriptomics allows the identification of disease- and cell-specific molecular signatures that may advance biomarker development and future treatments.</p><p>This study identified transcriptional signatures in keratinocytes and sub-basal CD4<sup>+</sup> and CD8<sup>+</sup> T lymphocytes from patients with psoriasis and AD. <em>In silico</em> prediction of ligand:receptor interactions delivered key signalling pathways (interferon, effector T cells, stroma cell and matrix biology, neuronal development, <em>etc.</em>). Targeted validation of selected transcripts, including CCL22, RELB, and JUND, in peripheral blood T cells suggests the chosen approach as a promising tool also in other inflammatory diseases.</p><p>Psoriasis and AD are characterized by transcriptional dysregulation in T cells and keratinocytes that may be targeted therapeutically. Spatial transcriptomics is a valuable tool in the search for molecular signatures that can be used as biomarkers and/or therapeutic targets.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110283"},"PeriodicalIF":8.6,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003929/pdfft?md5=cd23fd33b393b9c213d5242c41baf828&pid=1-s2.0-S1521661624003929-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330521","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

Spesolimab rapidly treats generalized pustular psoriasis and improves the skin immune microenvironment in Chinese patients 斯派索利单抗可快速治疗泛发性脓疱型银屑病并改善中国患者的皮肤免疫微环境。

IF 8.6 3区医学

Clinical immunology Pub Date : 2024-06-14 DOI: 10.1016/j.clim.2024.110280

Jiajing Lu , Qian Yu , Dawei Huang , Yifan Hu , Xiaoyuan Zhong , Jianfeng Zheng , Yangfeng Ding , Yunlu Gao , Ying Li , Yuling Shi

引用次数: 0

USP18 induction regulates immunometabolism to attenuate M1 signal-polarized macrophages and enhance IL-4-polarized macrophages in systemic lupus erythematosus USP18 诱导调节免疫代谢，以削弱系统性红斑狼疮中 M1 信号极化的巨噬细胞并增强 IL-4 极化的巨噬细胞。

IF 8.6 3区医学

Clinical immunology Pub Date : 2024-06-14 DOI: 10.1016/j.clim.2024.110285

Jenn-Haung Lai , De-Wei Wu , Chuan-Yueh Huang , Li-Feng Hung , Chien-Hsiang Wu , Ling-Jun Ho

{"title":"USP18 induction regulates immunometabolism to attenuate M1 signal-polarized macrophages and enhance IL-4-polarized macrophages in systemic lupus erythematosus","authors":"Jenn-Haung Lai , De-Wei Wu , Chuan-Yueh Huang , Li-Feng Hung , Chien-Hsiang Wu , Ling-Jun Ho","doi":"10.1016/j.clim.2024.110285","DOIUrl":"10.1016/j.clim.2024.110285","url":null,"abstract":"<div><p>Effective treatment of systemic lupus erythematosus (SLE) remains an unmet need. Different subsets of macrophages play differential roles in SLE and the modulation of macrophage polarization away from M1 status is beneficial for SLE therapeutics. Given the pathogenic roles of type I interferons (IFN-I) in SLE, this study investigated the effects and mechanisms of a mitochondria localization molecule ubiquitin specific peptidase 18 (USP18) preserving anti-IFN effects and isopeptidase activity on macrophage polarization. After observing USP18 induction in monocytes from SLE patients, we studied mouse bone marrow-derived macrophages and showed that USP18 deficiency increased M1signal (LPS + IFN-γ treatment)-induced macrophage polarization, and the effects involved the induction of glycolysis and mitochondrial respiration and the expression of several glycolysis-associated enzymes and molecules, such as hypoxia-inducible factor-1α. Moreover, the effects on mitochondrial activities, such as mitochondrial DNA release and mitochondrial reactive oxygen species production were observed. In contrast, the overexpression of USP18 inhibited M1signal-mediated and enhanced interleukin-4 (IL-4)-mediated polarization of macrophages and the related cellular events. Moreover, the levels of <em>USP18</em> mRNA expression showed tendency of correlation with the expression of metabolic enzymes in monocytes from patients with SLE. We thus concluded that by preserving anti-IFN effect and downregulating M1 signaling, promoting USP18 activity may serve as a useful approach for SLE therapeutics.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110285"},"PeriodicalIF":8.6,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330522","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

RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease RGC-32 在免疫介导的肾脏疾病中介导促炎症和坏死通路。

IF 8.6 3区医学

Clinical immunology Pub Date : 2024-06-13 DOI: 10.1016/j.clim.2024.110279

Alexandru Tatomir , Sonia Vlaicu , Vinh Nguyen , Irina G. Luzina , Sergei P. Atamas , Cinthia Drachenberg , John Papadimitriou , Tudor C. Badea , Horea G. Rus , Violeta Rus

{"title":"RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease","authors":"Alexandru Tatomir , Sonia Vlaicu , Vinh Nguyen , Irina G. Luzina , Sergei P. Atamas , Cinthia Drachenberg , John Papadimitriou , Tudor C. Badea , Horea G. Rus , Violeta Rus","doi":"10.1016/j.clim.2024.110279","DOIUrl":"10.1016/j.clim.2024.110279","url":null,"abstract":"<div><p>Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17<sup>+</sup> and IFNγ<sup>+</sup> cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. Thus, RGC-32 is a unique mediator shared by the Th17 and Th1 dependent proinflammatory and profibrotic pathways and a potential novel therapeutic target in the treatment of immune complex mediated glomerulonephritis such as lupus nephritis.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110279"},"PeriodicalIF":8.6,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327296","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

Alterations in exhausted and classical memory B cells in lupus nephritis – Relationship with disease relapse 狼疮性肾炎中衰竭和经典记忆 B 细胞的变化--与疾病复发的关系。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-06-13 DOI: 10.1016/j.clim.2024.110284

Litong Zhu , Yick Hei Wong , Sunny S.H. Wong , Simon C.Y. Cheung , Jason K.H. Sher , Irene Y.L. Yam , Susan Yung , Tak Mao Chan , Desmond Y.H. Yap

{"title":"Alterations in exhausted and classical memory B cells in lupus nephritis – Relationship with disease relapse","authors":"Litong Zhu , Yick Hei Wong , Sunny S.H. Wong , Simon C.Y. Cheung , Jason K.H. Sher , Irene Y.L. Yam , Susan Yung , Tak Mao Chan , Desmond Y.H. Yap","doi":"10.1016/j.clim.2024.110284","DOIUrl":"10.1016/j.clim.2024.110284","url":null,"abstract":"<div><h3>Introduction</h3><p>B cell exhaustion is a functional abnormality of B lymphocytes observed in chronic infections and shows association with autoreactivity. The role of exhausted and classical memory B cells in maintaining disease stability of lupus nephritis (LN) remains unclear.</p></div><div><h3>Methods</h3><p>We measured classical memory (CD19<sup>+</sup>CD21<sup>+</sup>CD27<sup>+</sup>), exhausted B cells (CD19<sup>+</sup>CD21<sup>−</sup>CD27<sup>−</sup>), and related cytokines in LN patients with multiple relapses (MR) (<em>n</em> = 15) and no relapse (NR) (n = 15) during disease remission. The expression of inhibitory/adhesion molecules, cell proliferation and calcium mobilization in classical memory and exhausted B cells were also assessed.</p></div><div><h3>Results</h3><p>The MR group had higher proportion of circulating exhausted and classical memory B cells compared to the NR group and healthy controls (HC) (p all <0.05 for MR vs. NR or HC). Blood levels of IL-6, BAFF, IL-21, CD62L, CXCR3 and Siglec-6 were all higher in the MR group (<em>p</em> < 0.05, for all). Exhausted B cells from the MR group showed higher FcRL4, CD22, CD85j and CD183 but lower CD62L expression than NR and HC groups. Exhausted B cells from MR patients exhibited reduced proliferation compared to NR patients and HC, while classical memory B cell proliferation in MR group was higher than the other two groups. Exhausted B cells from both MR and NR patients showed impaired calcium mobilization.</p></div><div><h3>Conclusion</h3><p>Alterations in exhausted and classical memory B cells are related to disease relapse in LN. These findings may help devise new strategies for monitoring disease activity and preventing relapse in LN.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110284"},"PeriodicalIF":4.5,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003930/pdfft?md5=11b0e15f4ee4915608200ebb30e145ec&pid=1-s2.0-S1521661624003930-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327295","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

NLRP12-associated autoinflammatory disease: A novel causal mutation and bioinformatics analyses NLRP12相关自身炎症性疾病：一种新的致病突变和生物信息学分析

IF 8.6 3区医学

Clinical immunology Pub Date : 2024-06-13 DOI: 10.1016/j.clim.2024.110278

Zhonghua Li , Qi Zhi , Jiahuang Li , Bo Zhu

{"title":"NLRP12-associated autoinflammatory disease: A novel causal mutation and bioinformatics analyses","authors":"Zhonghua Li , Qi Zhi , Jiahuang Li , Bo Zhu","doi":"10.1016/j.clim.2024.110278","DOIUrl":"https://doi.org/10.1016/j.clim.2024.110278","url":null,"abstract":"<div><p>Nucleotide-binding leucine-rich repeat-containing receptor 12-associated autoinflammatory disease (<em>NLRP12</em>-AID) is a rare autosomal dominant disorder. In this study, we reported a case of this rare disease with a novel <em>NLRP12</em> mutation (A218V, rs749659859). The patient displayed typical symptoms, including recurrent fever, arthralgia, and skin allergies. Elevated serum IgE, decreased apolipoprotein A1, high-density lipoprotein cholesterol, and fluctuating levels of various leukocyte subtypes, procalcitonin, IL6, creatine kinase, and 25-hydroxyvitamin D were also detected. Inflammatory lesions were observed in multiple organs using <sup>18</sup>F-FDG PET/CT. By mining single-cell transcriptome data, we identified relatively high expression of <em><em>NLRP12</em></em> in monocytes compared to other human peripheral blood mononuclear cells. <em>NLRP12</em>-positive monocytes exhibited reduced expression of <em>IL18</em>, <em>CCL3</em>, and <em>TNFA</em> compared to <em>NLRP12</em>-negative monocytes. Structural analyses suggested that the A218V mutation, along with A218T and F402L, may reduce the ATP-binding affinity of the NLRP12 protein. These findings may provide new insights into the mechanisms of <em>NLRP12</em>-AID, and suggest the potential ATP-based therapy for further investigation.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110278"},"PeriodicalIF":8.6,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141325179","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

T cell subset composition differs between blood and cerebrospinal fluid in amyotrophic lateral sclerosis 肌萎缩性脊髓侧索硬化症患者血液和脑脊液中的 T 细胞亚群组成不同。

IF 8.6 3区医学

Clinical immunology Pub Date : 2024-06-07 DOI: 10.1016/j.clim.2024.110270

Solmaz Yazdani , Anikó Lovik , Christina Seitz , Caroline Ingre , Fang Fang , John Andersson

引用次数: 0