Clinical immunology最新文献_第2页

Anti-C1s autoantibodies as complementary serologic biomarker in lupus nephritis 抗c1s自身抗体作为狼疮性肾炎的补充血清学生物标志物。

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-03-23 DOI: 10.1016/j.clim.2025.110487

Jeanne Vigne , Nolwenn Haut , Giovanna Clavarino , Noémie Jourde-Chiche , Françoise Sarrot-Reynauld , Leendert A. Trouw , Federica Defendi , Nicole M. Thielens , Christine Gaboriaud , Véronique Rossi , Chantal Dumestre-Pérard

{"title":"Anti-C1s autoantibodies as complementary serologic biomarker in lupus nephritis","authors":"Jeanne Vigne , Nolwenn Haut , Giovanna Clavarino , Noémie Jourde-Chiche , Françoise Sarrot-Reynauld , Leendert A. Trouw , Federica Defendi , Nicole M. Thielens , Christine Gaboriaud , Véronique Rossi , Chantal Dumestre-Pérard","doi":"10.1016/j.clim.2025.110487","DOIUrl":"10.1016/j.clim.2025.110487","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the presence of circulating autoantibodies. Autoantibodies targeting C1 complex proteins, particularly C1q, have already been described in lupus nephritis (LN). However, autoantibodies targeting the C1s protease remain poorly studied. We determined the prevalence of anti-C1s autoantibodies in serum of SLE patients, and evaluated their presence in relation to clinical conditions. For this purpose, sera from 187 SLE patients with different disease activity were selected and anti-C1s autoantibodies were measured by ELISA. We observed that patients with LN had significantly higher levels of anti-C1s autoantibodies than SLE patients with other flare types. Anti-C1s autoantibodies recognised mainly the C1s N-terminal part. Interestingly, the combination of anti-C1s, anti-DNA and anti-C1q autoantibodies showed high specificity (94.6 %) and a significant positive predictive value of 80 %. These results suggest the potential interest of anti-C1s autoantibodies as a complementary serological biomarker in the early screening for LN.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110487"},"PeriodicalIF":4.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708916","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

T cell aging and exhaustion: Mechanisms and clinical implications T细胞老化和衰竭：机制和临床意义。

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-03-20 DOI: 10.1016/j.clim.2025.110486

Weiqi Zhang , Dejun Kong , Xiaohan Zhang , Lu Hu , Yeqi Nian , Zhongyang Shen

{"title":"T cell aging and exhaustion: Mechanisms and clinical implications","authors":"Weiqi Zhang , Dejun Kong , Xiaohan Zhang , Lu Hu , Yeqi Nian , Zhongyang Shen","doi":"10.1016/j.clim.2025.110486","DOIUrl":"10.1016/j.clim.2025.110486","url":null,"abstract":"<div><div>T cell senescence and exhaustion represent critical aspects of adaptive immune system dysfunction, with profound implications for health and the development of disease prevention and therapeutic strategies. These processes, though distinct, are interconnected at the molecular level, leading to impaired effector functions and reduced proliferative capacity of T cells. Such impairments increase susceptibility to diseases and diminish the efficacy of vaccines and treatments. Importantly, T cell senescence and exhaustion can dynamically influence each other, particularly in the context of chronic diseases. A deeper understanding of the molecular mechanisms underlying T cell senescence and exhaustion, as well as their interplay, is essential for elucidating the pathogenesis of related diseases and restoring dysfunctional immune responses. This knowledge will pave the way for the development of targeted therapeutic interventions and strategies to enhance immune competence. This review aims to summarize the characteristics, mechanisms, and disease associations of T cell senescence and exhaustion, while also delineating the distinctions and intersections between these two states to enhance our comprehension.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110486"},"PeriodicalIF":4.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691188","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

Diffuse large B cell lymphoma in rheumatoid arthritis patients is associated with elevated B-cell driving factors including CXCL13 类风湿关节炎患者弥漫性大B细胞淋巴瘤与包括CXCL13在内的B细胞驱动因子升高有关。

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-03-19 DOI: 10.1016/j.clim.2025.110476

Nora Euler , Erik Hellbacher , Erik af Klint , Monika Hansson , Anders Larsson , Gunilla Enblad , Vivianne Malmström , Eva Baecklund , Caroline Grönwall , the AUTO-LYMPHOMA study group

{"title":"Diffuse large B cell lymphoma in rheumatoid arthritis patients is associated with elevated B-cell driving factors including CXCL13","authors":"Nora Euler , Erik Hellbacher , Erik af Klint , Monika Hansson , Anders Larsson , Gunilla Enblad , Vivianne Malmström , Eva Baecklund , Caroline Grönwall , the AUTO-LYMPHOMA study group","doi":"10.1016/j.clim.2025.110476","DOIUrl":"10.1016/j.clim.2025.110476","url":null,"abstract":"<div><div>Patients with rheumatoid arthritis (RA) are at increased risk of diffuse large B cell lymphoma (DLBCL) compared to the general population. Here, we explored the inflammatory profiles in the blood of RA patients who had developed DLBCL. RA-DLBCL patients had significantly higher levels of the pro-inflammatory markers TNF, IL-8, CXCL9, APRIL, and particularly CXCL13 (median 796 vs. 206 pg/mL, <em>p</em> = 0.001), compared to RA controls. By including an extensive autoantibody panel of rheumatoid factor, IgG anti-CCP2, anti-citrullinated protein antibodies (ACPA) fine-specificities, and other anti-modified protein antibodies, all RA-DLBCL patients were autoantibody seropositive. Yet, RA-DLBCL patients did not display significantly different autoantibody signatures compared to RA controls. The levels of immunoglobulin free light chains and C-reactive protein were similar in RA-DLBCL patients and RA controls. In conclusion, RA-DLBCL patients exhibit pro-inflammatory signatures with elevated markers that are important for B cells and may contribute to enhanced B-cell activation and promote lymphoma development.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110476"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673291","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

An analysis of the clinical value of CHI3L1 as a biomarker of multiple myeloma progression CHI3L1作为多发性骨髓瘤进展生物标志物的临床价值分析。

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-03-19 DOI: 10.1016/j.clim.2025.110474

Langui Tang , Juan Liang , Yazhou Huang , Kaiyun Guo , Yanzhao Huang , Yuxing He , Jun Wang , Ming Lei

{"title":"An analysis of the clinical value of CHI3L1 as a biomarker of multiple myeloma progression","authors":"Langui Tang , Juan Liang , Yazhou Huang , Kaiyun Guo , Yanzhao Huang , Yuxing He , Jun Wang , Ming Lei","doi":"10.1016/j.clim.2025.110474","DOIUrl":"10.1016/j.clim.2025.110474","url":null,"abstract":"<div><h3>Background</h3><div>The aim of this study was to systematically assess the relationship between Chitinase 3-like protein-1 (CHI3L1) protein and disease progression in multiple myeloma (MM) and to explore its potential clinical value as a biomarker to provide a basis for optimizing treatment strategies.</div></div><div><h3>Methods</h3><div>136 patients with MM were divided into two groups according to the efficacy: group 1–95 patients with non-progressing MM; group 2–41 patients with progressing MM. The concentration of CHI3L1 in the serum of the patients was determined by enzyme-linked immunosorbent assay (ELISA).</div></div><div><h3>Results</h3><div>CHI3L1 concentration in patients' serum was significantly greater than in healthy controls (<em>P</em> < 0.001), which patients with International Staging System (ISS) III had significantly higher CHI3L1 concentration than those with stage I/II. Patients in the progressed group had significantly higher CHI3L1 concentration than those in the non-progressed group by comparative analyses. Otherwise, multifactorial logistic regression analyses showed that CHI3L1 concentration was an independent predictor of MM progression after other confounding factors were excluded, and that the risk of progression in the high-concentration group was increased by 243.6 %, relative to the low-concentration group. Moreover, smoothed curve fitting analysis further confirmed that serum CHI3L1 concentration was linearly related to the probability of progression in MM patients, and the risk of progression increased as CHI3L1 concentration increased.</div></div><div><h3>Conclusions</h3><div>This study indicated that CHI3L1 concentration in the serum of MM patients was closely correlated with disease severity. High concentration CHI3L1 predicted the progression of MM disease, suggesting its clinical application potential in predicting disease prognosis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110474"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673288","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

Total plasma cfDNA methylation in pediatric kidney transplant recipients provides insight into acute allograft rejection pathophysiology 儿童肾移植受者血浆总cfDNA甲基化提供了急性同种异体移植排斥病理生理的见解。

IF 4.5 3区医学

Clinical immunology Pub Date : 2025-03-17 DOI: 10.1016/j.clim.2025.110475

Benjamin L. Spector , Boryana S. Koseva , Drinnan Sante , Warren A. Cheung , Reid S. Alisch , Alexander Kats , Phillip Bergmann , Elin Grundberg , Gerald J. Wyckoff , Laurel K. Willig

{"title":"Total plasma cfDNA methylation in pediatric kidney transplant recipients provides insight into acute allograft rejection pathophysiology","authors":"Benjamin L. Spector , Boryana S. Koseva , Drinnan Sante , Warren A. Cheung , Reid S. Alisch , Alexander Kats , Phillip Bergmann , Elin Grundberg , Gerald J. Wyckoff , Laurel K. Willig","doi":"10.1016/j.clim.2025.110475","DOIUrl":"10.1016/j.clim.2025.110475","url":null,"abstract":"<div><div>Cell-free DNA (cfDNA) is a marker of organ injury and immune response. DNA methylation is an epigenetic regulator of gene expression. Here, we elucidate total plasma cfDNA methylation from kidney transplant recipients in presence versus absence of rejection. In doing so, we exploit cfDNA as a real-time biomarker to define molecular pathways of rejection. Twenty plasma cfDNA samples from pediatric kidney transplant recipients were collected at allograft biopsy. Differentially methylated cytosine residues (>20 % methylation difference, <em>q</em>-value <0.05) were identified in presence (<em>N</em> = 7) versus absence (<em>N</em> = 9) of acute rejection. Separate analyses were performed comparing borderline rejection (<em>N</em> = 4) to rejection and non-rejection. In rejection versus non-rejection, there were 1269 differentially methylated genes corresponding to 533 pathways. These numbers were 4-13× greater than comparisons against borderline samples. Enriched pathways between rejection and non-rejection samples were related to immune cell/inflammatory response, lipid metabolism, and tryptophan-kynurenine metabolism, suggesting differential methylation of these pathways contributes to rejection.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110475"},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662964","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

Multi-omics integration and machine learning identify and validate neutrophil extracellular trap-associated gene signatures in chronic rhinosinusitis with nasal polyps 多组学集成和机器学习识别和验证慢性鼻窦炎伴鼻息肉的中性粒细胞细胞外陷阱相关基因特征

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 IL-4改变狼疮患者tlr7诱导的B细胞发育程序。

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 自身抗体的产生与COVID-19的临床严重程度相关：一项队列研究

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 JAK抑制剂改善IKZF1单倍不全患者的炎症性肠病

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 IKAROS蛋白的稳定性受其早期n端和c端二聚化结构域的调控。

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