{"title":"质控细胞仪发现法布里病的记忆 CD4 T 成熟明显受损,CD4 T 细胞中与 Gb3 相关的 CD27 表达不正常","authors":"Wladimir Mauhin, Gaelle Dzangue-Tchoupou, Damien Amelin, Aurélien Corneau, Foudil Lamari, Yves Allenbach, Bertrand Dussol, Vanessa Leguy-Seguin, Pauline D'Halluin, Marie Matignon, François Maillot, Kim-Heang Ly, Gérard Besson, Marjolaine Willems, Fabien Labombarda, Agathe Masseau, Christian Lavigne, Didier Lacombe, Hélène Maillard, Olivier Lidove, Olivier Benveniste","doi":"10.1002/jimd.12727","DOIUrl":null,"url":null,"abstract":"<p>Fabry disease (FD) is an X-linked disease characterized by an accumulation of glycosphingolipids, notably of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) leading to renal failure, cardiomyopathy, and cerebral strokes. Inflammatory processes are involved in the pathophysiology. We investigated the immunological phenotype of peripheral blood mononuclear cells in Fabry patients depending on the clinical phenotype, treatment, Gb3, and lysoGb3 levels and the presence of anti-drug antibodies (ADA). Leucocytes from 41 male patients and 20 controls were analyzed with mass cytometry using both unsupervised and supervised algorithms. FD patients had an increased expression of CD27 and CD28 in memory CD45- and CD45 + CCR7-CD4 T cells (respectively <i>p</i> < 0.014 and <i>p</i> < 0.02). Percentage of CD45RA-CCR7-CD27 + CD28+ cells in CD4 T cells was correlated with plasma lysoGb3 (<i>r</i> = 0.60; <i>p</i> = 0.0036) and phenotype (<i>p</i> < 0.003). The correlation between Gb3 and CD27 in CD4 T cells almost reached significance (<i>r</i> = 0.33; <i>p</i> = 0.058). There was no immune profile associated with the presence of ADA. Treatment with agalsidase beta was associated with an increased proportion of Natural Killer cells. These findings provide valuable insights for understanding FD, linking Gb3 accumulation to inflammation, and proposing new prognostic biomarkers.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"47 4","pages":"818-833"},"PeriodicalIF":4.2000,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mass cytometry reveals atypical immune profile notably impaired maturation of memory CD4 T with Gb3-related CD27 expression in CD4 T cells in Fabry disease\",\"authors\":\"Wladimir Mauhin, Gaelle Dzangue-Tchoupou, Damien Amelin, Aurélien Corneau, Foudil Lamari, Yves Allenbach, Bertrand Dussol, Vanessa Leguy-Seguin, Pauline D'Halluin, Marie Matignon, François Maillot, Kim-Heang Ly, Gérard Besson, Marjolaine Willems, Fabien Labombarda, Agathe Masseau, Christian Lavigne, Didier Lacombe, Hélène Maillard, Olivier Lidove, Olivier Benveniste\",\"doi\":\"10.1002/jimd.12727\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Fabry disease (FD) is an X-linked disease characterized by an accumulation of glycosphingolipids, notably of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) leading to renal failure, cardiomyopathy, and cerebral strokes. Inflammatory processes are involved in the pathophysiology. We investigated the immunological phenotype of peripheral blood mononuclear cells in Fabry patients depending on the clinical phenotype, treatment, Gb3, and lysoGb3 levels and the presence of anti-drug antibodies (ADA). Leucocytes from 41 male patients and 20 controls were analyzed with mass cytometry using both unsupervised and supervised algorithms. FD patients had an increased expression of CD27 and CD28 in memory CD45- and CD45 + CCR7-CD4 T cells (respectively <i>p</i> < 0.014 and <i>p</i> < 0.02). Percentage of CD45RA-CCR7-CD27 + CD28+ cells in CD4 T cells was correlated with plasma lysoGb3 (<i>r</i> = 0.60; <i>p</i> = 0.0036) and phenotype (<i>p</i> < 0.003). The correlation between Gb3 and CD27 in CD4 T cells almost reached significance (<i>r</i> = 0.33; <i>p</i> = 0.058). There was no immune profile associated with the presence of ADA. Treatment with agalsidase beta was associated with an increased proportion of Natural Killer cells. These findings provide valuable insights for understanding FD, linking Gb3 accumulation to inflammation, and proposing new prognostic biomarkers.</p>\",\"PeriodicalId\":16281,\"journal\":{\"name\":\"Journal of Inherited Metabolic Disease\",\"volume\":\"47 4\",\"pages\":\"818-833\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-04-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inherited Metabolic Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jimd.12727\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inherited Metabolic Disease","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jimd.12727","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
摘要
法布里病(Fabry disease,FD)是一种 X 连锁疾病,其特征是糖磷脂的积累,特别是球藻糖基甘油酰胺(Gb3)和球藻糖基鞘氨醇苷(lysoGb3)的积累,从而导致肾功能衰竭、心肌病和脑卒中。炎症过程参与了病理生理学。我们研究了法布里患者外周血单核细胞的免疫表型,这取决于临床表型、治疗、Gb3 和 lysoGb3 水平以及抗药物抗体(ADA)的存在。采用无监督和有监督算法对 41 名男性患者和 20 名对照组的白细胞进行了质谱分析。FD 患者的记忆 CD45- 和 CD45 + CCR7-CD4 T 细胞中 CD27 和 CD28 表达增加(分别为 p < 0.014 和 p < 0.02)。CD45RA-CCR7-CD27 + CD28+ 细胞在 CD4 T 细胞中的百分比与血浆溶菌酶 Gb3(r = 0.60;p = 0.0036)和表型(p <;0.003)相关。CD4 T 细胞中的 Gb3 与 CD27 之间的相关性几乎达到显著水平(r = 0.33;p = 0.058)。没有发现与 ADA 存在相关的免疫特征。使用阿加西酶 beta 治疗与自然杀伤细胞比例增加有关。这些发现为了解 FD、将 Gb3 积累与炎症联系起来以及提出新的预后生物标志物提供了宝贵的见解。
Mass cytometry reveals atypical immune profile notably impaired maturation of memory CD4 T with Gb3-related CD27 expression in CD4 T cells in Fabry disease
Fabry disease (FD) is an X-linked disease characterized by an accumulation of glycosphingolipids, notably of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) leading to renal failure, cardiomyopathy, and cerebral strokes. Inflammatory processes are involved in the pathophysiology. We investigated the immunological phenotype of peripheral blood mononuclear cells in Fabry patients depending on the clinical phenotype, treatment, Gb3, and lysoGb3 levels and the presence of anti-drug antibodies (ADA). Leucocytes from 41 male patients and 20 controls were analyzed with mass cytometry using both unsupervised and supervised algorithms. FD patients had an increased expression of CD27 and CD28 in memory CD45- and CD45 + CCR7-CD4 T cells (respectively p < 0.014 and p < 0.02). Percentage of CD45RA-CCR7-CD27 + CD28+ cells in CD4 T cells was correlated with plasma lysoGb3 (r = 0.60; p = 0.0036) and phenotype (p < 0.003). The correlation between Gb3 and CD27 in CD4 T cells almost reached significance (r = 0.33; p = 0.058). There was no immune profile associated with the presence of ADA. Treatment with agalsidase beta was associated with an increased proportion of Natural Killer cells. These findings provide valuable insights for understanding FD, linking Gb3 accumulation to inflammation, and proposing new prognostic biomarkers.
期刊介绍:
The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).