Clinical immunology最新文献_第2页

Multi-omics integration and machine learning identify and validate neutrophil extracellular trap-associated gene signatures in chronic rhinosinusitis with nasal polyps

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-03-13 DOI: 10.1016/j.clim.2025.110473

Fu Shu , Yaping Wang , Linglong Li , Lei Shi , Feng Zhang , Zhixuan Ma , Dehong Mao

{"title":"Multi-omics integration and machine learning identify and validate neutrophil extracellular trap-associated gene signatures in chronic rhinosinusitis with nasal polyps","authors":"Fu Shu , Yaping Wang , Linglong Li , Lei Shi , Feng Zhang , Zhixuan Ma , Dehong Mao","doi":"10.1016/j.clim.2025.110473","DOIUrl":"10.1016/j.clim.2025.110473","url":null,"abstract":"<div><div>This study aimed to explore the molecular characteristics of neutrophil extracellular traps (NETs) in chronic rhinosinusitis with nasal polyps (CRSwNP). Differentially expressed gene analysis, weighted gene co-expression network analysis, and machine learning algorithms identified three core NETs-associated genes: CXCR4, CYBB, and PTAFR, which were significantly upregulated in CRSwNP patients. The diagnostic performance of these genes was evaluated using receiver operating characteristic (ROC) curves, and their clinical relevance was validated using multicenter data. Immune infiltration analysis showed strong correlations between these genes and neutrophil and immune cell infiltration. Single-cell RNA sequencing demonstrated that these genes were predominantly expressed in myeloid and immune cells and exhibited dynamic changes during disease progression. These genes may contribute to CRSwNP pathogenesis through IL-17 signaling and metabolism-related pathways. This study identifies novel biomarkers and therapeutic targets for precise diagnosis and personalized treatment of CRSwNP.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110473"},"PeriodicalIF":4.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629370","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

IL-4 alters TLR7-induced B cell developmental program in lupus

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-03-09 DOI: 10.1016/j.clim.2025.110472

Changming Lu , Shanrun Liu , Min Gao , Jose Rubio , W. Winn Chatham , Hui-Chen Hsu , John D. Mountz

{"title":"IL-4 alters TLR7-induced B cell developmental program in lupus","authors":"Changming Lu , Shanrun Liu , Min Gao , Jose Rubio , W. Winn Chatham , Hui-Chen Hsu , John D. Mountz","doi":"10.1016/j.clim.2025.110472","DOIUrl":"10.1016/j.clim.2025.110472","url":null,"abstract":"<div><div>TLR7 stimulation of T-bet<sup>+</sup>CD11c<sup>+</sup>IgD<sup>−</sup>CD27<sup>−</sup> double-negative 2 (DN2) B cells is crucial for autoantibody formation in systemic lupus erythematosus (SLE). Here, we show that administration of IL-4 for five weeks significantly reduced autoantibodies and T-bet<sup>+</sup>CD11c<sup>+</sup> IgD<sup>−</sup> B cells in autoimmune BXD2 mice treated with R848, a TLR7 agonist. Single-cell transcriptomics analysis indicates that following two doses of <em>in vivo</em> administration, IL-4 redirected development toward follicular, CD23<sup>+</sup> germinal center (GC), and DN4-like memory B cells compared to treatment with R848 alone. While IL-4 enhanced genes related to antigen processing and presentation, it also suppressed R848-induced Ki67<sup>+</sup> GC B cells <em>in vivo</em>. <em>In vitro</em> stimulation of SLE patient B cells with a DN2 polarizing cocktail revealed that IL-4 reduced the expression of interferon response and DN2 signature genes, promoting a population of CD23<sup>+</sup>T-bet<sup>−</sup> DN4 B population. These findings suggest that developmental reprogramming by IL-4 counteracts TLR7-promoted DN2 and GC B cells in SLE.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110472"},"PeriodicalIF":4.5,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604214","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

Autoantibody development is associated with clinical severity of COVID-19: A cohort study

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-03-03 DOI: 10.1016/j.clim.2025.110471

Marie Brinkmann , Ludwig Traby , Manuel Kussmann , Matthias Weiss-Tessbach , Nina Buchtele , Thomas Staudinger , Elias Gaidoschik , Thomas Perkmann , Helmuth Haslacher , Franz Ratzinger , Winfried F. Pickl , Karim El-Gedawi , Melanie Feichter , Ellen Gelpi , Romana Höftberger , Peter Quehenberger , Rodrig Marculescu , Daniel Mrak , Kastriot Kastrati , Helga Lechner-Radner , Lisa Göschl

{"title":"Autoantibody development is associated with clinical severity of COVID-19: A cohort study","authors":"Marie Brinkmann , Ludwig Traby , Manuel Kussmann , Matthias Weiss-Tessbach , Nina Buchtele , Thomas Staudinger , Elias Gaidoschik , Thomas Perkmann , Helmuth Haslacher , Franz Ratzinger , Winfried F. Pickl , Karim El-Gedawi , Melanie Feichter , Ellen Gelpi , Romana Höftberger , Peter Quehenberger , Rodrig Marculescu , Daniel Mrak , Kastriot Kastrati , Helga Lechner-Radner , Lisa Göschl","doi":"10.1016/j.clim.2025.110471","DOIUrl":"10.1016/j.clim.2025.110471","url":null,"abstract":"<div><div>Viral infections, including respiratory diseases such as Coronavirus disease 2019 (COVID-19), are hypothesized to contribute to the onset of autoimmune disorders. Although elevated levels of autoantibodies have been observed following COVID-19, the role of specific autoantibodies linked to autoimmune diseases and their correlation with disease severity remains poorly defined.</div><div>In this study, we used a comprehensive autoantibody panel to assess the autoantibody production across different cohorts of COVID-19 patients, categorized by disease severity. We also compared patients with severe COVID-19 to a control group with other severe, non-COVID-related diseases.</div><div>Our findings indicate that the severity of COVID-19 corresponds to the overall production of specific autoantibodies, which are particularly associated with COVID-19. This association might predispose to an increased risk for the development of autoimmune conditions after a severe course of COVID-19.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"274 ","pages":"Article 110471"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548331","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

JAK inhibitor ameliorates inflammatory bowel disease in a patient with IKZF1 haploinsufficiency

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-03-02 DOI: 10.1016/j.clim.2025.110470

Shota Inoue , Masaatsu Ikai , Ryusuke Nambu , Kunihiko Moriya , Ryo Kojima , Yuji Tagami , Yuki Hoshino , Masashi Kyushiki , Kayoko Ichimura , Atsuko Nakazawa , Akihiro Hoshino , Takeshi Isoda , Hirokazu Kanegane , Kohsuke Imai

{"title":"JAK inhibitor ameliorates inflammatory bowel disease in a patient with IKZF1 haploinsufficiency","authors":"Shota Inoue , Masaatsu Ikai , Ryusuke Nambu , Kunihiko Moriya , Ryo Kojima , Yuji Tagami , Yuki Hoshino , Masashi Kyushiki , Kayoko Ichimura , Atsuko Nakazawa , Akihiro Hoshino , Takeshi Isoda , Hirokazu Kanegane , Kohsuke Imai","doi":"10.1016/j.clim.2025.110470","DOIUrl":"10.1016/j.clim.2025.110470","url":null,"abstract":"<div><div>IKAROS, encoded by <em>IKZF1</em>, is a crucial transcription factor regulating hematopoiesis and B cell development. While <em>IKZF1</em> haploinsufficiency variants are associated with various immunological disorders, inflammatory bowel disease (IBD) has been rarely reported. We report a case of <em>IKZF1</em> haploinsufficiency presenting with an atypical IBD phenotype and its response to filgotinib. The patient was previously diagnosed with <em>IKZF</em>1 haploinsufficiency and presented with chronic diarrhea, fatigue and anemia. Laboratory findings indicated folate deficiency-induced megaloblastic anemia and malabsorption syndrome. Endoscopic examination showed inflammation with erythema in the colon and extensive villous blunting of the small intestine. Immunohistochemical analysis revealed increased pSTAT3/5 in the colon. Considering the clinical features and increased JAK-STAT cascade, treatment with filgotinib was initiated. At 10 weeks post-treatment, we observed improvement in endoscopic findings and suppression of pSTAT3/5. This case extends the clinical spectrum of <em>IKZF1</em> haploinsufficiency. A JAK1 inhibitor is considered to be useful for <em>IKZF1</em> haploinsufficiency-associated IBD.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"274 ","pages":"Article 110470"},"PeriodicalIF":4.5,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548330","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

IKAROS protein stability is regulated by its early N-terminal region and C-terminal dimerization domain

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-02-28 DOI: 10.1016/j.clim.2025.110469

Natchanun Klangkalya , Ana Esteve-Sole , Agustin A. Gil Silva , Jennifer L. Stoddard , Julie E. Niemela , Seraina Prader , Gregor Dueckers , Lina Igel , Tim Niehues , Benjamin C. Stewart-Bates , Talal Mousallem , Thomas A. Fleisher , Sergio D. Rosenzweig , Hye Sun Kuehn

{"title":"IKAROS protein stability is regulated by its early N-terminal region and C-terminal dimerization domain","authors":"Natchanun Klangkalya , Ana Esteve-Sole , Agustin A. Gil Silva , Jennifer L. Stoddard , Julie E. Niemela , Seraina Prader , Gregor Dueckers , Lina Igel , Tim Niehues , Benjamin C. Stewart-Bates , Talal Mousallem , Thomas A. Fleisher , Sergio D. Rosenzweig , Hye Sun Kuehn","doi":"10.1016/j.clim.2025.110469","DOIUrl":"10.1016/j.clim.2025.110469","url":null,"abstract":"<div><div>IKAROS, encoded by <em>IKZF1</em>, is a six zinc-finger (ZF) transcription factor integral to lymphocyte development and function. <em>IKZF1</em> mutations affecting DNA-binding (ZF1–4) and dimerization (ZF5–6) have been extensively reported and result in human disease. Herein, we investigated <em>IKZF1</em> mutations affecting protein stability.</div><div>We identified ten individuals in three families carrying <em>IKZF1</em> mutations mapping either to the pre-ZF1 area (D22N), or the dimerization domain (M494Vfs*86, Y503*) presenting with infections, immune dysregulation and/or lymphoproliferation with incomplete clinical penetrance. IKAROS expression was reduced in all mutation-carrier evaluated. Protein stability was decreased for D22N, V52L (another pre-ZF1 variant reported in COSMIC), Y503* and Del1–116, a laboratory-designed mutant encompassing the pre-ZF1 area. Mutants Y503* and Del1–116 also exhibited other impaired functions. IKAROS N-terminal pre-ZF1 area, encompassing a previously uncharacterized protein stability-associated region (PSAR), is crucial for IKAROS stability. Variants in the IKAROS PSAR leading to decreased protein stability and IKAROS haploinsufficiency seem sufficient to result in immune defects and IKAROS-associated diseases.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"274 ","pages":"Article 110469"},"PeriodicalIF":4.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536832","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

New biomarkers in IgA nephropathy IgA 肾病的新生物标记物

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-02-27 DOI: 10.1016/j.clim.2025.110468

Zhixin Xu , Haoting Zhan , Jingdi Zhang, Zhan Li, Linlin Cheng, Qian Chen, Ye Guo, Yongzhe Li

引用次数: 0

Spatial transcriptomics of Glomerulo-centric antibody mediated rejection in renal transplants

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-02-22 DOI: 10.1016/j.clim.2025.110460

Dajana Margeta , Hirotsugu Noguchi , Sepideh Khazaie , Leal C. Herlitz , Joshua J. Augustine , Peter S. Heeger , Anat R. Tambur , Robert L. Fairchild , William M. Baldwin III

{"title":"Spatial transcriptomics of Glomerulo-centric antibody mediated rejection in renal transplants","authors":"Dajana Margeta , Hirotsugu Noguchi , Sepideh Khazaie , Leal C. Herlitz , Joshua J. Augustine , Peter S. Heeger , Anat R. Tambur , Robert L. Fairchild , William M. Baldwin III","doi":"10.1016/j.clim.2025.110460","DOIUrl":"10.1016/j.clim.2025.110460","url":null,"abstract":"<div><div>In this case study, we used Digital Spatial Profiling to localize transcripts in a series of 4 biopsies from a single patient before, during and after treatment for acute antibody-mediated rejection that was characterized by strong C4d staining of the glomeruli. Spatial resolution demonstrated that molecular signatures of innate immune cells including NK cells and macrophages are located in glomeruli during AMR, and transcripts for HLA class II antigens were upregulated in the glomeruli. In contrast, transcripts of signature genes for podocytes were decreased during rejection. Treatment with IVIg resolved histological evidence of glomerulitis but did not restore expression of podocyte transcripts. These data demonstrate a vulnerability of podocytes in acute AMR with persistent glomerulitis. Additionally, by using a protocol biopsy from the same patient as a baseline, transcript changes for an informative set of genes were uncovered to test for podocyte dysfunction in future patients.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"274 ","pages":"Article 110460"},"PeriodicalIF":4.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487986","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 efficacy and safety between efgartigimod and intravenous immunoglobulin in elderly generalized myasthenia gravis patients

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-02-21 DOI: 10.1016/j.clim.2025.110457

Chaoyue Zhang , Xiang Li , Yufei Deng , Haocheng Luo , Shuangshuang Wang , Xianni Yan , Xiaojun Yang , Qilong Jiang

引用次数: 0

Complement C5a and C5a receptor 1 mediates glomerular damage in focal segmental glomerulosclerosis

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-02-19 DOI: 10.1016/j.clim.2025.110459

Xiao-jie Gong , Jing Huang , Yue Shu , Miao Wang , Jing Ji , Li Yang , Ming-hui Zhao , Zhao Cui

{"title":"Complement C5a and C5a receptor 1 mediates glomerular damage in focal segmental glomerulosclerosis","authors":"Xiao-jie Gong , Jing Huang , Yue Shu , Miao Wang , Jing Ji , Li Yang , Ming-hui Zhao , Zhao Cui","doi":"10.1016/j.clim.2025.110459","DOIUrl":"10.1016/j.clim.2025.110459","url":null,"abstract":"<div><h3>Background</h3><div>Clinical data and animal models have provided compelling evidence supporting the pathogenic role of complement activation in the progression of focal segmental glomerulosclerosis (FSGS). However, the mechanisms underlying complement-induced podocyte injury and parietal epithelial cell (PEC) activation are not well understood.</div></div><div><h3>Methods</h3><div>We evaluated glomerular C5aR1 (CD88) expression in FSGS patients and tested the effects of the C5aR1 antagonist (PMX205) in Adriamycin nephropathy mice. The effects on PECs and podocytes were evaluated following exposure to recombinant C5a or FSGS plasma, with or without the C5aR1 antagonist.</div></div><div><h3>Results</h3><div>C5aR1 was overexpressed on PECs and podocytes in FSGS patients, with levels positively correlated with serum creatinine, the percentage of segmental glomerulosclerosis, and the prognosis of refractory nephrotic syndrome. In Adriamycin nephropathy mice, the C5aR1 antagonist significantly attenuated proteinuria, blood urea nitrogen levels, and the percentage of segmental and global glomerulosclerosis. It also alleviated PEC activation and proliferation, and mitigated podocyte loss. Moreover, glomerular IgM deposits were reduced, followed by decreased deposits of C3d and C5b-9. In vitro, PECs exposed to recombinant C5a exhibited upregulated expression of CD44 and Notch1, along with increased secretion of COL4A2. Podocytes exposed to FSGS plasma showed impaired cell viability and downregulation of synaptopodin, effects that were reversed by the C5aR1 antagonist.</div></div><div><h3>Conclusions</h3><div>These findings highlight the pathogenic role of the complement system in the development of FSGS through the C5a-C5aR1 axis on podocytes and PECs. The C5aR1 antagonist represents a promising therapeutic intervention for FSGS patients.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"273 ","pages":"Article 110459"},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454181","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

Plasma extracellular vesicles promote follicular T helper cell expansion in primary Sjögren's syndrome

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-02-18 DOI: 10.1016/j.clim.2025.110458

Suying Liu , Chaowen Luo , Chengmei He , Jinlei Sun , Zhilei Chen , Taibiao Lyu , Lin Qiao , Fengchun Zhang , Hua Chen

引用次数: 0