Genes and immunity最新文献_第2页

Neutrophil extracellular traps formation driven by novel ELANE mutations in cyclic neutropenia patients 中性粒细胞胞外陷阱形成由新的ELANE突变驱动的循环中性粒细胞减少症患者。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-06-23 DOI: 10.1038/s41435-026-00403-4

Magdalena Rutkowska-Zapała, Adrianna Gałuszka-Bulaga, Jacek Plewka, Marzena Lenart, Anna Kluczewska, Marta Surman, Karolina Bukowska-Strakova, Monika Rygielska, Izabela Siemińska, Katarzyna Baran, Joanna Cichy, Joanna Skrzeczyńska-Moncznik, Jarosław Baran, Maciej Siedlar, Anna Szaflarska

{"title":"Neutrophil extracellular traps formation driven by novel ELANE mutations in cyclic neutropenia patients","authors":"Magdalena Rutkowska-Zapała, Adrianna Gałuszka-Bulaga, Jacek Plewka, Marzena Lenart, Anna Kluczewska, Marta Surman, Karolina Bukowska-Strakova, Monika Rygielska, Izabela Siemińska, Katarzyna Baran, Joanna Cichy, Joanna Skrzeczyńska-Moncznik, Jarosław Baran, Maciej Siedlar, Anna Szaflarska","doi":"10.1038/s41435-026-00403-4","DOIUrl":"10.1038/s41435-026-00403-4","url":null,"abstract":"Cyclic neutropenia (CyN) is a rare haematological disorder most often caused by mutations in the neutrophil elastase gene (ELANE). We describe three novel ELANE mutations in CyN patients and link them to impaired neutrophil extracellular trap (NET) formation. ELANE sequencing was performed using the Sanger method, and AlphaFold2 was used to visualize the impact of mutations on the structure of neutrophil elastase (NE). NET formation was assessed by colocalization of MPO, NE, and DNA using fluorescence microscopy, and free DNA was quantified fluorometrically. We identified two missense substitutions (M66K, V133G) and one deletion (G192-G196del). These mutations did not significantly alter the overall NE structure but exhibited functional effects: M66K may disrupt substrate binding, V133G increases protein mobility, and the Deletion of G192-G196 may limit the opening of the catalytic pocket. NETosis was impaired in CyN patients compared with controls. Their NETs appeared less expanded, and DNA release into supernatants was reduced, reaching the lowest levels during neutropenia, even in patients with normal neutrophil counts. These abnormalities were accompanied by reduced NE activity. In sum, novel ELANE variants may contribute to altered NE function and defective NET formation in CyN, suggesting that impaired NETosis is partly independent of cyclic changes in neutrophil numbers.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"475-486"},"PeriodicalIF":4.2,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307940","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

Immunogenetics in psoriasis: towards personalised diagnosis and treatment strategies 银屑病的免疫遗传学：个性化诊断和治疗策略。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-05-13 DOI: 10.1038/s41435-026-00402-5

Dineshwar Sugumaran, Audrey Chee Hui Yong, Kang Nien How, Johnson Stanslas

{"title":"Immunogenetics in psoriasis: towards personalised diagnosis and treatment strategies","authors":"Dineshwar Sugumaran, Audrey Chee Hui Yong, Kang Nien How, Johnson Stanslas","doi":"10.1038/s41435-026-00402-5","DOIUrl":"10.1038/s41435-026-00402-5","url":null,"abstract":"Psoriasis is an autoimmune disorder, and about 125 million people worldwide suffer from this chronic skin disease. It is a multifactorial disorder influenced by the combined action of many genetic factors and their interactions with environmental factors. Recently, significant advances in research have provided greater insight into the pathophysiologic mechanisms, highlighting the roles of genetic susceptibility loci such as HLA-C*06:02, IL12B, and TNIP1, as well as immune pathways involving IL-17, IL-23, and TNF-α. These discoveries not only provided a better understanding of psoriasis but also played a vital role in developing treatment strategies. This review highlights immunological and genetic insights of psoriasis, emphasising their translational relevance. The review also covers how genetic variations modulate the immune response, leading to disease occurrence and chronicity. Moreover, the article explores how these findings are shaping personalised diagnosis and treatment strategies. This strategy holds the promise of enhancing the treatment of individuals with psoriasis by transitioning from the traditional care paradigm to patient-centred care in dermatology.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"385-400"},"PeriodicalIF":4.2,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928613","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

Hyperactivation of the cGAS-STING pathway promotes liver inflammation in Down syndrome cGAS-STING通路的过度激活促进唐氏综合征的肝脏炎症。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-05-02 DOI: 10.1038/s41435-026-00401-6

Aashirwad Shahi, Nyima Kinteh, Julia A. Goewey Ruiz, Jonathan D. Santoro, Lekidelu Taddesse-Heath, Dawit Kidane

{"title":"Hyperactivation of the cGAS-STING pathway promotes liver inflammation in Down syndrome","authors":"Aashirwad Shahi, Nyima Kinteh, Julia A. Goewey Ruiz, Jonathan D. Santoro, Lekidelu Taddesse-Heath, Dawit Kidane","doi":"10.1038/s41435-026-00401-6","DOIUrl":"10.1038/s41435-026-00401-6","url":null,"abstract":"Patients with Down Syndrome (DS) are characterized by dysfunction of several organs, including the liver, brain, heart defects, gastrointestinal anomalies, and lethal immune hypersensitivity. A person with DS is also susceptible to various inflammatory diseases, including hepatic autoimmune diseases. The Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is known to trigger the stimulator of interferon genes (STING) and downstream proinflammatory factors. In this work, we hypothesized that oxidative stress-associated DNA damage triggers activation of the cGAS-STING signaling pathway and promotes liver inflammation in DS. Here, we investigated the role of reactive oxygen species (ROS) associated DNA damage and the cGAS-STING signaling pathway in the pathogenesis of hepatic inflammation in the DS model. Our results showed that DS cells harbor excessive ROS and DNA damage in DS fibroblasts and DS mouse liver. Further, DS cells accumulate micronuclei that likely serve as a source of cytoplasmic DNA to stimulate cGAS-STING activation. In addition, RNA-seq analysis results showed enhanced expression of key type I interferon factors in cGAS-STING pathways in DS liver and inflammatory responses and elevated liver enzymes such as alanine transaminase (ALT) that indicate a hepatocellular liver injury in DS. The results of this study opened the opportunity to connect endogenous DNA damage triggers innate immune response, which may contribute to the upregulation of the cGAS-STING signaling to exacerbate hepatic inflammation in DS.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"466-474"},"PeriodicalIF":4.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814240","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

Immunological and prognostic impact of NRF2 in high grade serous ovarian cancer NRF2在高级别浆液性卵巢癌中的免疫学和预后影响。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-04-28 DOI: 10.1038/s41435-026-00400-7

Samera H. Hamad, Chelsea Katz, Helen Toma, Kosuke Murakami, Nasrine Bendjilali, Gord Zhu, Hadi Shojaei, Lanlan Fang, Samuel Leung, Martin Koebel, Huseyin Karaduman, Oliver Abinader, Ramkrishna Mitra, Lauren Krill, Christina Chu, David P. Warshal, Yemin Wang

{"title":"Immunological and prognostic impact of NRF2 in high grade serous ovarian cancer","authors":"Samera H. Hamad, Chelsea Katz, Helen Toma, Kosuke Murakami, Nasrine Bendjilali, Gord Zhu, Hadi Shojaei, Lanlan Fang, Samuel Leung, Martin Koebel, Huseyin Karaduman, Oliver Abinader, Ramkrishna Mitra, Lauren Krill, Christina Chu, David P. Warshal, Yemin Wang","doi":"10.1038/s41435-026-00400-7","DOIUrl":"10.1038/s41435-026-00400-7","url":null,"abstract":"NRF2 modulates tumor immune microenvironment in several cancers. NRF2 is activated in about 50% of high-grade serous ovarian cancer (HGSOC), the most aggressive type of ovarian cancer. Through analyzing data from scRNA-seq (n = 7), bulk RNA-seq (n = 365), and tumor microarray (TMA) of human HGSOC (n = 240) samples, we demonstrated that NRF2 expression correlated with tumor immune microenvironment in HGSOC. Functional pathway enrichment analysis and transcription factors (TFs) prediction showed the functional relevance of NRF2 expression in shaping the immune phenotype of HGSOC. Pathways such as hedgehog and ROS signaling, and TFs including EGR1, ESRRA, SMAD proteins, and SP-family proteins, are implicated in the immune suppressive microenvironment of NRF2High tumors. Immune differentiation analysis showed patients with NRF2High tumors enriched with CD68 have lower survival (p = 0.038) than those with CD68Low tumors, whereas NRF2Low tumors enriched with immune-activated markers such as CD3E and CD80 exhibit a better prognosis. This study is the first that shows classification of HGSOC based on NRF2 levels, highlights new biomarkers, and suggests IHC-labeling and genomic evaluation of NRF2 and immune markers for better prognosis.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"456-465"},"PeriodicalIF":4.2,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769042","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

RASSF2 promoter hypermethylation determines malignant and microenvironmental features in lung cancer RASSF2启动子超甲基化决定肺癌的恶性和微环境特征。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-04-22 DOI: 10.1038/s41435-026-00398-y

Yingying Han, Wenying Jiang, Qingning Chen, Junpu Wang, Chunlin Ou

{"title":"RASSF2 promoter hypermethylation determines malignant and microenvironmental features in lung cancer","authors":"Yingying Han, Wenying Jiang, Qingning Chen, Junpu Wang, Chunlin Ou","doi":"10.1038/s41435-026-00398-y","DOIUrl":"10.1038/s41435-026-00398-y","url":null,"abstract":"Complexity of the microenvironment of lung adenocarcinoma (LUAD) poses significant challenges in its clinical management. Systematic bioinformatic analysis of the Ras-association domain family (RASSF) identified RASSF2 as a potential tumour suppressor in LUAD. This study aims to investigate its clinical significance and functional mechanisms in LUAD. CCK-8, EdU, and colony formation assays were performed to investigate the impact of RASSF2 overexpression on the proliferative capacity of LUAD cells. Transwell and wound healing assays were performed to explore the significance of RASSF2 on LUAD cell migration and invasion. RNA sequencing analysis was conducted on three methylation-positive and three methylation-negative LUAD tissue samples to establish the underlying mechanism of RASSF2 methylation in LUAD. Functional studies indicated that RASSF2 overexpression significantly inhibited the proliferation, migration, and invasion of LUAD cells. Patients with RASSF2 promoter hypermethylation exhibited a significantly shorter overall survival than those without. RNA-seq of three pairs of LUAD tissue samples further demonstrated that RASSF2 methylation is associated with upregulation of the NF-κB signalling pathway and dysregulation of T-cell activation pathways. This study confirmed the tumour-suppressive role of RASSF2 in LUAD and suggests its potential as an immunotherapeutic target, thus providing new insights into LUAD treatment strategies.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"427-443"},"PeriodicalIF":4.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769152","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

Secreted SULF1 protein modulates CD8 + T cell exhaustion by promoting TAM polarization in gastric cancer 胃癌中分泌的SULF1蛋白通过促进TAM极化调节CD8 + T细胞耗竭。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-04-15 DOI: 10.1038/s41435-026-00399-x

Xiaodan Lu, Di Lu

{"title":"Secreted SULF1 protein modulates CD8 + T cell exhaustion by promoting TAM polarization in gastric cancer","authors":"Xiaodan Lu, Di Lu","doi":"10.1038/s41435-026-00399-x","DOIUrl":"10.1038/s41435-026-00399-x","url":null,"abstract":"Gastric cancer (GC) progression is linked to immune escape in the tumor microenvironment, yet the molecules regulating tumor-associated macrophage polarization and CD8+ T-cell exhaustion are unclear. This study analyzed TCGA data to examine SULF1 expression and its prognostic role. It used CRISPR/Cas9 and lentiviral methods in GC cells to test proliferation, invasion, and apoptosis, plus co-culture and flow cytometry to assess SULF1’s impact on macrophages and CD8+ T-cells. STAT3 signaling was studied via immunoblotting and nuclear translocation assays, and a mouse model tested SULF1’s therapeutic relevance. Results showed SULF1 was up-regulated in GC, tied to advanced stages and poor survival. SULF1 knockdown inhibited the malignant phenotypes of gastric cancer cells, including proliferation, migration, and invasion abilities, while promoting cell apoptosis; conversely, SULF1 overexpression enhanced these pro-tumor phenotypes. SULF1 activated macrophage STAT3, promoting M2 polarization and CD8+ T-cell dysfunction. In mice, SULF1 silencing reduced tumors and T-cell exhaustion, while supplementation reversed this. Conclusions: GC-secreted SULF1 creates an immunosuppressive microenvironment via STAT3-dependent pathways, and targeting SULF1–STAT3 may improve GC immunity.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"444-455"},"PeriodicalIF":4.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689727","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

Single-cell mapping of peripheral immune dynamics in pregnant women after Moderna mRNA COVID-19 vaccination 孕妇接种新冠病毒mRNA后外周血免疫动力学单细胞定位

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-04-14 DOI: 10.1038/s41435-026-00394-2

Yu-Ting Kang, Tsai-Jung Lu, Po-Liang Cheng, Li-Wen Lee, Pei-Pei Jhan, Yi-Ming Chen, Tzu-Hung Hsiao

{"title":"Single-cell mapping of peripheral immune dynamics in pregnant women after Moderna mRNA COVID-19 vaccination","authors":"Yu-Ting Kang, Tsai-Jung Lu, Po-Liang Cheng, Li-Wen Lee, Pei-Pei Jhan, Yi-Ming Chen, Tzu-Hung Hsiao","doi":"10.1038/s41435-026-00394-2","DOIUrl":"10.1038/s41435-026-00394-2","url":null,"abstract":"Pregnant individuals are at increased risk of severe outcomes from COVID-19 infection, yet the immune responses elicited by vaccination during pregnancy remain poorly understood. In this study, longitudinal single-cell RNA sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells from three pregnant women at four time points: before vaccination, one and two weeks after the first dose of the Moderna mRNA vaccine, and after the second dose postpartum. Dynamic immune changes, including a transient increase in inflammatory classical monocytes (cM_1) after the first dose, marked by elevated expression of IL1B, NLRP3 and NFKB1, as well as moderate activation of interferon-stimulated genes were observed. CD4⁺ T cells exhibited activation and differentiation into memory subsets. By contrast, B cell responses were minimal after the first dose, and enhanced protein synthesis activity emerged only after the second dose, which suggested delayed humoral activation. Although limited by sample size, our findings indicate that vaccination in pregnancy induces a nonexcessive innate immune activation, coordinated T cell responses and attenuated B cell activity that likely reflect pregnancy-driven immunoregulatory adaptations. These findings reveal the immune dynamics following mRNA vaccination during pregnancy and highlight the importance of developing vaccination strategies tailored for pregnant individuals.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 3","pages":"374-383"},"PeriodicalIF":4.5,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41435-026-00394-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689790","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

Retraction Note: Predictable regulation of gut microbiome in immunotherapeutic efficacy of gastric cancer 注：肠道微生物组在胃癌免疫治疗疗效中的可预测调节。

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-04-02 DOI: 10.1038/s41435-026-00397-z

Wei Gao, Xinli Wang, Yi Shi, Guangfeng Wu, Min Zhou, Xiaoyan Lin

引用次数: 0

FOLR3+neutrophils contribute to sepsis by exacerbating hyper-inflammation FOLR3+中性粒细胞通过加剧过度炎症导致败血症。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-04-01 DOI: 10.1038/s41435-026-00396-0

Fangchao Chen, Hongyu Tan, Dianyang Wang, Rui Su, Jiaxiang Liao, Hongfei Ge, Wei Wang

{"title":"FOLR3+neutrophils contribute to sepsis by exacerbating hyper-inflammation","authors":"Fangchao Chen, Hongyu Tan, Dianyang Wang, Rui Su, Jiaxiang Liao, Hongfei Ge, Wei Wang","doi":"10.1038/s41435-026-00396-0","DOIUrl":"10.1038/s41435-026-00396-0","url":null,"abstract":"Sepsis severity is associated with sustained neutrophilia, yet the underlying heterogeneity remains unclear. By integrating single-cell and bulk RNA-seq of septic peripheral blood, we uncovered five neutrophils clusters. FOLR3+neutrophils were the predominant and terminally differentiated subgroup, which displayed hyper-inflammatory signatures and low HLA expression, especially in non-survivors of sepsis. Cell-chat analysis also showed these neutrophils could promote sepsis progression by recruiting platelet via RETN-CAP1 and NAMPT-ITGB1 axes. External validation found that higher FOLR3+neutrophils were associated with 28-day mortality of sepsis. Transcription-factor and pseudotime analyses identified HIF-1A as the key driver of FOLR3+neutrophils specification. In vitro experiments validated that FOLR3 expression and HIF-1A were also found to be higher in sepsis. Over-expression or knockout of HIF-1A in patient and mouse neutrophils confirmed direct control of HIF-1A on secretion of IL-1β, TNF-α, IL-8 and IL-6. In conclusion, FOLR3+neutrophils contribute to sepsis prognosis by exacerbating hyper-inflammation and FOLR3 may serve as a new promising prognostic biomarker for sepsis.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"410-426"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591689","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

Longitudinal omics reveals immune repertoire remodeling in myasthenia gravis patients post-tacrolimus therapy 纵向组学揭示重症肌无力患者在他克莫司治疗后的免疫系统重构。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-03-30 DOI: 10.1038/s41435-026-00395-1

Ting He, Liu Wang, Kangzhi Chen, Qian Zhou, Liqun Xu, Zhaohui Luo, Huan Yang

{"title":"Longitudinal omics reveals immune repertoire remodeling in myasthenia gravis patients post-tacrolimus therapy","authors":"Ting He, Liu Wang, Kangzhi Chen, Qian Zhou, Liqun Xu, Zhaohui Luo, Huan Yang","doi":"10.1038/s41435-026-00395-1","DOIUrl":"10.1038/s41435-026-00395-1","url":null,"abstract":"Myasthenia gravis (MG) is a T/B cell-driven autoimmune disease. The immunomodulatory mechanisms of the common immunosuppressant tacrolimus (TAC) on the immune repertoire are unclear. This study investigated TAC’s immunomodulatory effects via high-throughput sequencing of peripheral blood mononuclear cells from four MG patients pre- and post-four months of TAC monotherapy, revealing dynamic T-cell receptor (TCR) and B-cell receptor (BCR) repertoire remodeling. The immune repertoire of MG patients was characterized by a skewed usage of TRBV gene families compared to healthy controls, indicating an underlying immune dysfunction. Longitudinal analysis post-TAC therapy revealed potential downregulation of IGHV1-69 and IGHV3-43 gene frequencies (p < 0.05, FDR > 0.1), alongside non-significant trends toward shorter CDR3 lengths and reduced clonal diversity in both IGH and TRB (p > 0.05). The BCR repertoire underwent greater dynamic remodeling, while the TCR repertoire remained relatively stable, as evidenced by the persistence of dominant clones and overlapping TRB clones. BCR diversity and V or J gene usage in TCR and BCR showed potential associations with clinical severity. These data reveal skewed antigen recognition profiles in MG pathogenesis, with TAC orchestrating multimodal immunomodulation through peripheral immune repertoire reshaping.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"401-409"},"PeriodicalIF":4.2,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581022","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