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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 Q2 IMMUNOLOGY Pub Date : 2024-06-13 DOI: 10.1016/j.clim.2024.110278
Zhonghua Li , Qi Zhi , Jiahuang Li , Bo Zhu

Nucleotide-binding leucine-rich repeat-containing receptor 12-associated autoinflammatory disease (NLRP12-AID) is a rare autosomal dominant disorder. In this study, we reported a case of this rare disease with a novel NLRP12 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 18F-FDG PET/CT. By mining single-cell transcriptome data, we identified relatively high expression of NLRP12 in monocytes compared to other human peripheral blood mononuclear cells. NLRP12-positive monocytes exhibited reduced expression of IL18, CCL3, and TNFA compared to NLRP12-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 NLRP12-AID, and suggest the potential ATP-based therapy for further investigation.

核苷酸结合富亮氨酸重复受体 12 相关自身炎症性疾病(NLRP12-AID)是一种罕见的常染色体显性遗传疾病。在这项研究中,我们报告了一例患有新型 NLRP12 基因突变(A218V,rs749659859)的罕见病例。患者表现出典型症状,包括反复发热、关节痛和皮肤过敏。血清 IgE 升高,脂蛋白 A1 和高密度脂蛋白胆固醇降低,各种白细胞亚型、降钙素原、IL6、肌酸激酶和 25- 羟维生素 D 水平波动。使用18F-FDG PET/CT在多个器官中观察到炎症病变。通过挖掘单细胞转录组数据,我们发现与其他人类外周血单核细胞相比,NLRP12在单核细胞中的表达相对较高。与 NLRP12 阴性的单核细胞相比,NLRP12 阳性的单核细胞表现出 IL18、CCL3 和 TNFA 的低表达。结构分析表明,A218V 突变以及 A218T 和 F402L 可能会降低 NLRP12 蛋白的 ATP 结合亲和力。这些发现可能会对 NLRP12-AID 的机制提供新的见解,并建议进一步研究基于 ATP 的潜在疗法。
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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 Q2 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

Inflammation is a hallmark of amyotrophic lateral sclerosis (ALS) and is often assessed through biological samples. Due to the easier access, peripheral blood is more commonly phenotyped instead of cerebrospinal fluid (CSF) or affected tissues in ALS. Here, using flow cytometry, we compared the composition of T cell subsets in blood and CSF in ALS patients. We found consistent but weak correlations between blood and CSF for all T cell subsets examined. This finding implies that blood and CSF offer complementary information when characterizing T cell immunity in ALS and blood may not be used as a surrogate for CSF.

炎症是肌萎缩性脊髓侧索硬化症(ALS)的标志,通常通过生物样本进行评估。由于更容易获得,外周血而不是脑脊液(CSF)或 ALS 患者的受累组织更常被进行表型分析。在这里,我们使用流式细胞术比较了 ALS 患者血液和 CSF 中 T 细胞亚群的组成。我们发现血液和脑脊液中的所有 T 细胞亚群之间存在一致但微弱的相关性。这一发现意味着,在描述 ALS 的 T 细胞免疫特征时,血液和 CSF 可提供互补信息,而血液不可用作 CSF 的替代物。
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引用次数: 0
Exploring the HLA complex in autoimmunity: From the risk haplotypes to the modulation of expression 探索自身免疫中的 HLA 复合物:从风险单倍型到表达调节。
IF 8.6 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-06-06 DOI: 10.1016/j.clim.2024.110266
Silvia Sartoris , Giovanna Del Pozzo

The genes mapping at the HLA region show high density, strong linkage disequilibrium and high polymorphism, which affect the association of HLA class I and class II genes with autoimmunity. We focused on the HLA haplotypes, genomic structures consisting of an array of specific alleles showing some degrees of genetic association with different autoimmune disorders. GWASs in many pathologies have identified variants in either the coding loci or the flanking regulatory regions, both in linkage disequilibrium in haplotypes, that are frequently associated with increased risk and may influence gene expression. We discuss the relevance of the HLA gene expression because the level of surface heterodimers determines the number of complexes presenting self-antigen and, thus, the strength of pathogenic autoreactive T cells immune response.

映射在 HLA 区域的基因显示出高密度、强连锁不平衡和高多态性,这影响了 HLA I 类和 II 类基因与自身免疫的关联。我们的研究重点是 HLA 单倍型,它是由一系列特定等位基因组成的基因组结构,与不同的自身免疫性疾病有一定程度的遗传关联。对许多病症进行的全球基因组研究发现,编码基因位点或侧翼调控区域的变异(两者在单倍型中处于连锁不平衡状态)经常与风险增加有关,并可能影响基因表达。我们讨论了 HLA 基因表达的相关性,因为表面异质二聚体的水平决定了呈现自身抗原的复合物的数量,从而决定了致病性自反应 T 细胞免疫反应的强度。
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引用次数: 0
Clinical features and lymphocyte immunophenotyping analysis in primary immunodeficiency patients with non-transplant lymphoproliferative disorders 原发性免疫缺陷患者非移植淋巴增生性疾病的临床特征和淋巴细胞免疫分型分析。
IF 8.6 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-06-04 DOI: 10.1016/j.clim.2024.110269
Wen-I Lee , Jing-Long Huang , Meng-Ying Hsieh , Li-Chen Chen , Kuo-Wei Yeh , Liang-Shiou Ou , Tsung-Chieh Yao , Chao-Yi Wu , Syh-Jae Lin , Shih-Hsiang Chen , Tang-Her Jaing , Chi-Jou Liang , Chen-Chen Kang

Lymphoproliferative disorders (LPD) comprise a heterogeneous group and are originally classified into the “Disease of immune dysregulation” category. Of 96 Taiwanese patients during 2003–2022, 31 (median 66, range 0.03–675 months) developed LPD, mainly including palpable lymphadenopathy (in 10 patients), intestinal lymphadenopathy associated with refractory inflammatory bowel disease (IBD in 8) and hepatosplenomegaly (in 7) during long-term follow-up (median 144, range 3–252 months). They distributed in the categories of antibody deficiency (2 CVID, 2 TTC37, PIK3CD, PIK3R1 and AICDA each), phagocyte (4 CYBB, 1 STAT1 and 1 IFNRG1), immune dysregulation (2 FOXP3, 2 XIAP and 2 HLH), combined immunodeficiencies (2 IL2RG; CD40L, ZAP70 and unknown each), syndromic features (2 STAT3-LOF, 1 WAS and 1 ATM) and three with anti-IFN-γ autoantibodies. An increased senescent (CD8 + CD57+) and CD21-low, disturbed transitional B (CD38 + IgM++), plasmablast B (CD38++IgM-), memory B (CD19 + CD27+) and TEMRA (CD27-IgD-) components were often observed in cross-sectional immunophenotyping and trended to develop LPD.

淋巴组织增生性疾病(LPD)是一种异质性疾病,最初被归类为 "免疫调节失调疾病"。2003-2022 年间,96 名台湾患者中有 31 人(中位数为 66 个月,范围为 0.03-675 个月)患上了淋巴增生性疾病,主要包括可触及的淋巴结病(10 人)、与难治性炎症性肠病(IBD)相关的肠道淋巴结病(8 人)以及长期随访期间(中位数为 144 个月,范围为 3-252 个月)出现的肝脾肿大(7 人)。他们分布在抗体缺乏(CVID 2 例、TTC37、PIK3CD、PIK3R1 和 AICDA 各 2 例)、吞噬细胞(CYBB 4 例、STAT1 1 例和 IFNRG1 1 例)、免疫失调(FOXP3 2 例、XIAP 2 例和 HLH 2 例)、联合免疫缺陷(IL2RG.CD40L.ZAP70 和 IL2RG.CD40L.ZAP70 各 2 例)和肝脾肿大等类别;CD40L、ZAP70 和未知)、综合征特征(2 例 STAT3-LOF、1 例 WAS 和 1 例 ATM)以及 3 例抗-IFN-γ 自身抗体。在横断面免疫分型中经常观察到衰老(CD8 + CD57+)和低 CD21、紊乱的过渡 B(CD38 + IgM++)、浆细胞 B(CD38++IgM-)、记忆 B(CD19 + CD27+)和 TEMRA(CD27-IgD-)成分增多,并有发展为 LPD 的趋势。
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引用次数: 0
Two novel compound heterozygous loss-of-function mutations cause fetal IRAK-4 deficiency presenting with Pseudomonas Aeruginosa sepsis 两种新型复合杂合功能缺失突变导致胎儿IRAK-4缺乏症,并伴有绿脓杆菌败血症。
IF 8.6 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-06-03 DOI: 10.1016/j.clim.2024.110268
Fang Zhang , Zhiwei Wang , Shuai Men, Jinglu Zhang, Leilei Wang

Purpose

To report a case of a five-month-old Chinese infant who died of interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency presenting with rapid and progressive Pseudomonas aeruginosa sepsis.

Methods

The genetic etiology of IRAK-4 deficiency was confirmed through trio-whole exome sequencing and Sanger sequencing. Functional consequences were invested using an in vitro minigene splicing assay.

Results

Trio-whole exome sequencing of genomic DNA identified two novel compound heterozygous mutations, IRAK-4 (NM_016123.3): c.942–1G > A and c.644_651+ 6delTTGCAGCAGTAAGT in the proband, which originated from his symptom-free parents. These mutations were predicted to cause frameshifts and generate three truncated proteins without enzyme activity.

Conclusions

Our findings expand the range of IRAK-4 mutations and provide functional support for the pathogenic effects of splice-site mutations. Additionally, this case highlights the importance of considering the underlying genetic defects of immunity when dealing with unusually overwhelming infections in previously healthy children and emphasizes the necessity for timely treatment with wide-spectrum antimicrobials.

目的:报告一例五个月大的中国婴儿因白细胞介素-1受体相关激酶-4(IRAK-4)缺乏症而死亡的病例:方法:通过三重全外显子组测序和桑格测序确认了IRAK-4缺乏症的遗传学病因。方法:通过三全外显子组测序和桑格测序确认了 IRAK-4 缺乏症的遗传学病因,并使用体外微型基因剪接试验对其功能性后果进行了研究:结果:基因组DNA的三重全外显子测序发现了两个新的复合杂合突变,即IRAK-4 (NM_016123.3):c.942-1G > A和c.644_651+ 6delTTGCAGCAGTAAGT。据预测,这些突变会导致框架转换,并产生三个没有酶活性的截短蛋白:我们的研究结果扩大了IRAK-4突变的范围,并为剪接位点突变的致病作用提供了功能性支持。此外,本病例还强调了在处理以往健康儿童异常严重的感染时考虑潜在的免疫遗传缺陷的重要性,并强调了及时使用广谱抗微生物药物治疗的必要性。
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引用次数: 0
Imbalance of SARS-CoV-2-specific CCR6+ and CXCR3+ CD4+ T cells and IFN-γ + CD8+ T cells in patients with Long-COVID 长COVID患者中SARS-CoV-2特异性CCR6+和CXCR3+ CD4+T细胞与IFN-γ + CD8+T细胞的失衡。
IF 8.6 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-05-31 DOI: 10.1016/j.clim.2024.110267
Pedro Martínez-Fleta , María Celeste Marcos , Daniel Jimenez-Carretero , José María Galván-Román , Rosa María Girón-Moreno , Ana Adela Calero-García , Ana Arcos-García , Enrique Martín-Gayo , Hortensia de la Fuente , Laura Esparcia-Pinedo , Javier Aspa , Julio Ancochea , Arantzazu Alfranca , Francisco Sánchez-Madrid

Long-COVID (LC) is characterised by persistent symptoms for at least 3 months after acute infection. A dysregulation of the immune system and a persistent hyperinflammatory state may cause LC. LC patients present differences in activation and exhaustion states of innate and adaptive compartments. Different T CD4+ cell subsets can be identified by differential expression of chemokine receptors (CCR). However, changes in T cells with expression of CCRs such as CCR6 and CXCR3 and their relationship with CD8+ T cells remains unexplored in LC. Here, we performed unsupervised analysis and found CCR6+ CD4+ subpopulations enriched in COVID-19 convalescent individuals upon activation with SARS-CoV-2 peptides. SARS-CoV-2 specific CCR6+ CD4+ are decreased in LC patients, whereas CXCR3+ CCR6- and CCR4+ CCR6- CD4+ T cells are increased. LC patients showed lower IFN-γ-secreting CD8+ T cells after stimulation with SARS-CoV-2 Spike protein. This work underscores the role of CCR6 in the pathophysiology of LC.

长期慢性乙型脑炎(Long-COVID,LC)的特征是急性感染后症状持续至少 3 个月。免疫系统失调和持续的高炎症状态可能会导致 LC。LC 患者的先天性免疫系统和适应性免疫系统的激活和衰竭状态存在差异。可以通过趋化因子受体(CCR)的不同表达来识别不同的 T CD4+ 细胞亚群。然而,在 LC 中,表达 CCR(如 CCR6 和 CXCR3)的 T 细胞的变化及其与 CD8+ T 细胞的关系仍未得到研究。在这里,我们进行了无监督分析,发现 COVID-19 康复者在被 SARS-CoV-2 多肽激活后,CCR6+ CD4+ 亚群富集。在 LC 患者中,SARS-CoV-2 特异性 CCR6+ CD4+ 减少,而 CXCR3+ CCR6- 和 CCR4+ CCR6- CD4+ T 细胞增加。LC 患者在受到 SARS-CoV-2 Spike 蛋白刺激后,分泌 IFN-γ 的 CD8+ T 细胞减少。这项研究强调了 CCR6 在 LC 病理生理学中的作用。
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引用次数: 0
The immunomodulatory of interleukin-33 in rheumatoid arthritis: A systematic review 白细胞介素-33 对类风湿性关节炎的免疫调节作用:系统综述。
IF 8.6 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-05-31 DOI: 10.1016/j.clim.2024.110264
Renli Liu, Fangfang Wang, Xing Luo, Fengfan Yang, Jie Gao, Haomiao Shen, Zhaohui Zheng

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that primarily affects the joints and surrounding soft tissues, characterized by chronic inflammation and proliferation of the synovium. Various immune cells are involved in the pathophysiology of RA. The complex interplay of factors such as chronic inflammation, genetic susceptibility, dysregulation of serum antibody levels, among others, contribute to the complexity of the disease mechanism, disease activity, and treatment of RA. Recently, the cytokine storm leading to increased disease activity in RA has gained significant attention. Interleukin-33 (IL-33), a member of the IL-1 family, plays a crucial role in inflammation and immune regulation. ST2 (suppression of tumorigenicity 2 receptor), the receptor for IL-33, is widely expressed on the surface of various immune cells. When IL-33 binds to its receptor ST2, it activates downstream signaling pathways to exert immunoregulatory effects. In RA, IL-33 regulates the progression of the disease by modulating immune cells such as circulating monocytes, tissue-resident macrophages, synovial fibroblasts, mast cells, dendritic cells, neutrophils, T cells, B cells, endothelial cells, and others. We have summarized and analyzed these findings to elucidate the pathways through which IL-33 regulates RA. Furthermore, IL-33 has been detected in the synovium, serum, and synovial fluid of RA patients. Due to inconsistent research results, we conducted a meta-analysis on the association between serum IL-33, synovial fluid IL-33, and the risk of developing RA in patients. The pooled SMD was 1.29 (95% CI: 1.15–1.44), indicating that IL-33 promotes the onset and pathophysiological progression of RA. Therefore, IL-33 may serve as a biomarker for predicting the risk of developing RA and treatment outcomes. As existing drugs for RA still cannot address drug resistance in some patients, new therapeutic approaches are needed to alleviate the significant burden on RA patients and healthcare systems. In light of this, we analyzed the potential of targeting the IL-33/ST2-related signaling pathway to modulate immune cells associated with RA and alleviate inflammation. We also reviewed IL-33 and RA susceptibility-related single nucleotide polymorphisms, suggesting potential involvement of IL-33 and macrophage-related drug-resistant genes in RA resistance therapy. Our review elucidates the role of IL-33 in the pathophysiology of RA, offering new insights for the treatment of RA.

类风湿性关节炎(RA)是一种全身性慢性自身免疫性疾病,主要影响关节和周围软组织,以滑膜的慢性炎症和增生为特征。各种免疫细胞参与了 RA 的病理生理学过程。慢性炎症、遗传易感性、血清抗体水平失调等因素的复杂相互作用,导致了 RA 的发病机制、疾病活动和治疗的复杂性。最近,导致 RA 疾病活动性增加的细胞因子风暴引起了广泛关注。白细胞介素-33(IL-33)是 IL-1 家族的成员之一,在炎症和免疫调节中发挥着至关重要的作用。IL-33的受体ST2(抑制肿瘤生成2受体)广泛表达于各种免疫细胞表面。当 IL-33 与其受体 ST2 结合时,会激活下游信号通路,从而发挥免疫调节作用。在 RA 中,IL-33 通过调节循环单核细胞、组织驻留巨噬细胞、滑膜成纤维细胞、肥大细胞、树突状细胞、中性粒细胞、T 细胞、B 细胞、内皮细胞等免疫细胞来调节疾病的进展。我们对这些发现进行了总结和分析,以阐明IL-33调节RA的途径。此外,在 RA 患者的滑膜、血清和滑液中也检测到了 IL-33。由于研究结果不一致,我们对血清IL-33、滑膜液IL-33与患者罹患RA风险之间的关系进行了荟萃分析。汇总的SMD为1.29(95% CI:1.15-1.44),表明IL-33会促进RA的发病和病理生理进展。因此,IL-33 可作为预测 RA 发病风险和治疗效果的生物标志物。由于现有的 RA 药物仍无法解决部分患者的耐药性问题,因此需要新的治疗方法来减轻 RA 患者和医疗系统的沉重负担。有鉴于此,我们分析了靶向 IL-33/ST2 相关信号通路以调节与 RA 相关的免疫细胞并缓解炎症的潜力。我们还回顾了IL-33和RA易感性相关的单核苷酸多态性,表明IL-33和巨噬细胞相关耐药基因可能参与RA耐药治疗。我们的综述阐明了IL-33在RA病理生理学中的作用,为RA的治疗提供了新的见解。
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引用次数: 0
Allergic bronchopulmonary aspergillosis in a lung transplant recipient treated with mepolizumab 一名肺移植受者在接受甲泼尼珠单抗治疗后出现过敏性支气管肺曲霉病。
IF 8.6 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-05-25 DOI: 10.1016/j.clim.2024.110265
Foteini Ioakeim , Christophe Abellan , Alessio Casutt , Benoit Lechartier , Leslie Noirez , Catherine Beigelman-Aubry , John-David Aubert , Zisis Balmpouzis , Angela Koutsokera

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus spp. ABPA diagnosis may be challenging due to its non-specific presentation. Standard ABPA treatment consists of systemic corticosteroids and antifungal agents. Mepolizumab, a monoclonal antibody against interleukin-5 seems to be a promising treatment for ABPA. Data about ABPA following lung transplantation (LuTx) are scarce. LuTx recipients are at higher risk for adverse effects of ABPA treatment compared to the general population.

Here we present a case of a LuTx recipient who was successfully treated with mepolizumab for ABPA following LuTx. Prolonged administration of high dose prednisone was thus avoided. To our knowledge, this is the first case describing mepolizumab administration following LuTx. Mepolizumab seems particularly attractive as a corticosteroid-sparing agent or as an alternative option to antifungal treatments, because of its excellent safety profile and low risk of drug interactions.

过敏性支气管肺曲霉菌病(ABPA)是一种对曲霉菌属的复杂超敏反应。标准的 ABPA 治疗包括全身使用皮质类固醇激素和抗真菌药物。抗白细胞介素-5 的单克隆抗体 Mepolizumab 似乎是治疗 ABPA 的一种很有前景的方法。有关肺移植(LuTx)后 ABPA 的数据很少。与普通人群相比,肺移植受者出现 ABPA 治疗不良反应的风险更高。在此,我们介绍了一例在肺移植术后使用甲泼尼单抗成功治疗 ABPA 的病例。因此避免了长期使用大剂量泼尼松。据我们所知,这是第一例描述 LuTx 术后使用美妥珠单抗的病例。由于美妥珠单抗具有极佳的安全性和较低的药物相互作用风险,因此作为一种皮质类固醇替代药物或抗真菌治疗的替代选择似乎特别有吸引力。
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引用次数: 0
Immune reconstitution and survival, following hematopoietic stem cell transplantation in Omani patients with inborn errors of immunity 阿曼先天性免疫错误患者造血干细胞移植后的免疫重建和存活率
IF 8.6 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-05-23 DOI: 10.1016/j.clim.2024.110263
Salem Al-Tamemi , Abdulhakim Al-Rawas , Murtadha Al-Khabori , Khalil Al-Farsi , Mohammed Al-Huneini , Amr Abdalla , Salam Al-Kindi , David Dennison

Background

Hematopoietic stem cell transplantation (HSCT) is a curative treatment for certain inborn errors of immunity.

Methods

A 17-year retrospective cohort study was conducted on 40 immunodeficient patients who underwent HSCT.

Results

The median age at transplant was 11.0 months (4.6–61.0). Donors were primarily matched sibling donors (60%). 90% and 85% of patients received conditioning and graft-versus-host disease (GVHD) prophylaxis, respectively. The mean donor chimerism at the last follow-up was 88.6% ± 17.9% (40–100). Median serum immunoglobulin (Ig) G level, CD4+ T-cell count, and CD19+ B-cell count were 11.7 g/L (9.2–13.6), 0.9 × 109/L 0.6–1.2), and 0.5 × 109/L (0.2–0.7), respectively. 29 patients (72.5%) received intravenous immunoglobulins (IVIG) therapy, with a median duration of 10.0 months (4.0–14.0). The median post-transplant follow-up was 6.5 years (IQR:1.4–11.5). The 10-year overall probability of survival is 84.3%.

Conclusion

Monitoring IRC is important in ensuring adequate disease-free survival.

背景造血干细胞移植(HSCT)是治疗某些先天性免疫错误的一种治愈性疗法。方法对40名接受造血干细胞移植的免疫缺陷患者进行了一项为期17年的回顾性队列研究。供体主要是匹配的同胞供体(60%)。90%和85%的患者分别接受了调理和移植物抗宿主病(GVHD)预防。最后一次随访时的平均供体嵌合率为 88.6% ± 17.9% (40-100)。血清免疫球蛋白(Ig)G水平、CD4+ T细胞计数和CD19+ B细胞计数的中位数分别为11.7克/升(9.2-13.6)、0.9×109/升(0.6-1.2)和0.5×109/升(0.2-0.7)。29名患者(72.5%)接受了静脉注射免疫球蛋白(IVIG)治疗,中位持续时间为10.0个月(4.0-14.0)。移植后随访的中位数为 6.5 年(IQR:1.4-11.5)。结论IRC的监测对于确保足够的无病生存期非常重要。
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引用次数: 0
Effects of anti-CD20 therapy on circulating and intrathecal follicular helper T cell subsets in multiple sclerosis 抗CD20疗法对多发性硬化症患者循环和鞘内滤泡辅助T细胞亚群的影响。
IF 8.6 3区 医学 Q2 IMMUNOLOGY Pub Date : 2024-05-23 DOI: 10.1016/j.clim.2024.110262
Sahla El Mahdaoui , Marie Mathilde Hansen , Malene Bredahl Hansen , Victoria Hyslop Hvalkof , Helle Bach Søndergaard , Mie Reith Mahler , Jeppe Romme Christensen , Finn Sellebjerg , Marina Rode von Essen

Follicular helper T (Tfh) cells and their interplay with B cells likely contribute to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). Tfh cells are enriched in cerebrospinal fluid (CSF) in RRMS, but effects of anti-CD20 therapy are unknown. We investigated Tfh cells in controls, untreated and anti-CD20-treated patients with RRMS using flow cytometry. CSF Tfh cells were increased in untreated patients. Compared to paired blood samples, CD25 Tfh cells were enriched in CSF in RRMS, but not in controls. Contrast-enhancing brain MRI lesions and IgG index correlated with CSF CD25 Tfh cell frequency in untreated patients with RRMS. Anti-CD20 therapy reduced the numbers of circulating PD1+ Tfh cells and CD25 Tfh cells, and the frequency of CSF CD25 Tfh cells. The study suggests that CD25 Tfh cells are recruited to the CSF in RRMS, associated with focal inflammation, and are reduced by anti-CD20 therapy.

滤泡辅助T细胞(Tfh)及其与B细胞的相互作用可能是复发缓解型多发性硬化症(RRMS)的发病机制之一。Tfh细胞在RRMS患者的脑脊液(CSF)中富集,但抗CD20治疗的效果尚不清楚。我们使用流式细胞术研究了对照组、未接受治疗和接受抗 CD20 治疗的 RRMS 患者的 Tfh 细胞。在未经治疗的患者中,CSF Tfh细胞有所增加。与配对血液样本相比,CD25- Tfh细胞在RRMS患者的CSF中富集,而在对照组中则没有富集。在未经治疗的RRMS患者中,对比增强的脑MRI病变和IgG指数与CSF中CD25- Tfh细胞的频率相关。抗CD20疗法减少了循环中PD1+ Tfh细胞和CD25- Tfh细胞的数量,也降低了CSF CD25- Tfh细胞的频率。该研究表明,CD25- Tfh细胞被招募到RRMS的CSF中,与病灶炎症有关,并通过抗CD20治疗而减少。
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Clinical immunology
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