Journal of Translational Autoimmunity最新文献_第3页

The significance of m6A-circFOXK2 in CD4+T cells from patients with rheumatoid arthritis and circFOXK2 correlates with Th17 % and autophagy m6A-circFOXK2在类风湿关节炎患者CD4+T细胞中的意义与th17%和自噬相关

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-10-15 DOI: 10.1016/j.jtauto.2025.100326

Qing Luo , Zhiwei Wu , Qiuyun Xiao , Mengfan Lan , Shiqian Wang , Peng Fu , Biqi Fu , Zikun Huang , Junming Li

Objective

CD4⁺T cells are significant compositions of immune cells in rheumatoid arthritis (RA) and the aberrant function of CD4⁺T cells have been demonstrated to promote RA's progression. N6-methyladenosine (m6A) is a highly enriched modification found in CircRNAs. However, the role of m6A-methylated circRNA in regulation of CD4⁺T cells function in RA and its association with RA disease activity are presently unclear.

Methods

We used m6A-circRNA epitranscriptomic microarray analysis and m6A RNA immunocoprecipitation-quantitative polymerase chain reaction (MeRIP-qPCR) to screen and verify the differentially expressed m6A-methylated circRNAs in CD4⁺T cells from RA and HC.

Results

Many m6A-methylated circRNAs were differentially expressed in patients with new-onset RA. M6A-methylated circFOXK2 in the CD4⁺T cells of patients with new-onset RA was significantly decreased, the expression level of circFOXK2 in the CD4⁺T cells of patients with new-onset RA was significantly increased and correlated with treatment, Th17 %, autophagy. CircFOXK2 could function as competing endogenous RNAs to regulate miR-486-3p expression. In many m6A regulators, only a-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) was significantly increased in the CD4⁺T cells of patients with new-onset RA, and its level positively correlated with rheumatoid factor, the expression of circFOXK2. Moreover, the change of ALKBH5 could affect the level of m6A and circFOXK2 in Jurkat cell line.

Conclusion

We indicated a notable decrease in the m6A-methylated level of circFOXK2 in CD4⁺T cells from human RA, indicating a potential role of hypomethylated circFOXK2 in CD4⁺T cells function and RA pathogenesis. This may show valuable insight into the ALKBH5/m6A-circFOXK2/miRNA interaction network and the mechanism of RA.

目的CD4+T细胞是类风湿关节炎（RA）免疫细胞的重要组成部分，CD4+T细胞的异常功能促进了RA的进展。n6 -甲基腺苷（m6A）是CircRNAs中发现的一种高度富集的修饰。然而，m6a甲基化circRNA在RA中调节CD4+T细胞功能的作用及其与RA疾病活动性的关系目前尚不清楚。方法采用m6A- circrna表转录组微阵列分析和m6A RNA免疫共沉淀-定量聚合酶链反应（MeRIP-qPCR）技术筛选和验证RA和HC患者CD4+T细胞中m6A-甲基化circrna的差异表达。结果许多m6a甲基化环状rna在新发RA患者中存在差异表达。m6a甲基化circFOXK2在新发RA患者CD4+T细胞中的表达水平显著降低，circFOXK2在新发RA患者CD4+T细胞中的表达水平显著升高，并与治疗、th17%、自噬相关。CircFOXK2可以作为竞争性内源性rna调节miR-486-3p的表达。在许多m6A调节因子中，只有a-酮戊二酸依赖性双加氧酶alkB同源物5 （ALKBH5）在新发RA患者的CD4+T细胞中显著升高，且其水平与类风湿因子、circFOXK2的表达呈正相关。此外，ALKBH5的变化可以影响Jurkat细胞株m6A和circFOXK2的水平。结论在RA患者的CD4+T细胞中，circFOXK2的m6a甲基化水平显著降低，提示circFOXK2低甲基化在CD4+T细胞功能和RA发病机制中可能发挥作用。这可能对ALKBH5/m6A-circFOXK2/miRNA相互作用网络和RA的机制提供有价值的见解。

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引用次数: 0

Novel variants in ARID1B, SPSB1, and RAET1-AS shape genetic susceptibility and protection in systemic lupus erythematosus and lupus nephritis ARID1B、SPSB1和RAET1-AS的新变异在系统性红斑狼疮和狼疮性肾炎中形成遗传易感性和保护作用

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-10-10 DOI: 10.1016/j.jtauto.2025.100322

Hung-Yi Chen , Feng-Cheng Liu , Hsian-Cheng Chen , Tan-Mei Liu , Fu-Chiang Yeh , Yu-Tien Chang

Background

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune dysregulation affecting multiple organs, most notably lupus nephritis (LN). Genetic susceptibility significantly contributes to disease severity and prognosis. However, genomic studies specific to Taiwanese SLE patients, particularly those focusing on LN, remain limited. This study aimed to identify genetic variants associated with SLE and LN in a Taiwanese cohort.

Methods

Genome-wide association studies (GWAS) were performed on 276 Taiwanese SLE patients compared with 3393 patients with other rheumatic diseases. Single-nucleotide polymorphism (SNP) genotyping was conducted using the Taiwan Precision Medicine Array, with analyses adjusted for age, sex, and population structure. Functional annotations and biomarkers of renal function were assessed for identified SNPs.

Results

Compared with patients with other rheumatic diseases, a novel protective variant, rs9480438 (ARID1B), was identified in the SLE group, suggesting an association with dysregulation of cell cycle checkpoints. In the LN group, a protective variant, rs1294028 (SPSB1), and a risk variant, rs17079029 (RAET1-G/RAET1-AS), were linked to altered serum biomarkers and potential pathogenesis influenced by TGFβ and NK cells.

Conclusions

Novel genetic variants related to immune regulation and autoimmunity in Taiwanese SLE and LN patients were identified. These variants provide insight into disease mechanisms and may guide early detection and personalized therapeutic approaches.

系统性红斑狼疮（SLE）是一种以影响多器官的免疫失调为特征的自身免疫性疾病，最显著的是狼疮肾炎（LN）。遗传易感性对疾病严重程度和预后有显著影响。然而，针对台湾SLE患者的基因组研究，特别是针对LN的研究，仍然有限。本研究旨在找出台湾人群中与SLE和LN相关的遗传变异。方法对276例台湾SLE患者与3393例其他风湿病患者进行全基因组关联研究（GWAS）。采用台湾精密医学阵列进行单核苷酸多态性（SNP）基因分型，并根据年龄、性别和人口结构进行调整。对鉴定出的snp进行肾功能功能注释和生物标志物的评估。结果与其他风湿病患者相比，在SLE组中发现了一种新的保护性变异rs9480438 (ARID1B)，提示与细胞周期检查点失调有关。在LN组中，一种保护性变异rs1294028 （SPSB1）和一种风险变异rs17079029 （RAET1-G/RAET1-AS）与血清生物标志物的改变和TGFβ和NK细胞影响的潜在发病机制有关。结论台湾SLE和LN患者存在与免疫调节和自身免疫相关的新基因变异。这些变异提供了对疾病机制的深入了解，并可能指导早期发现和个性化治疗方法。

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引用次数: 0

TGF-β1 promotes collagen synthesis in systemic sclerosis via upregulating P4HA3 TGF-β1通过上调P4HA3促进系统性硬化症的胶原合成

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-10-06 DOI: 10.1016/j.jtauto.2025.100323

Zhaopeng Chen , Yinru Lin , Yayi Huang , Zhixian Chen , Yao Gong , Zhiduo Hou , Ling Lin

Objective

Systemic sclerosis (SSc) is a complex autoimmune disease resulting in fibrosis of skin and internal organs. Despite progress in treatment, SSc carries high mortality due to organ fibrosis. This study aimed to identify a potential antifibrotic therapeutic for the treatment of SSc.

Methods

SSc bioinformatics data (GSE181549 and GSE138669) were obtained from the public Gene Expression Omnibus (GEO) database. Subsequently, we conducted differential analysis, Protein–protein interaction (PPI) network construction, gene enrichment analysis to identify a key fibrotic gene, followed by verification.

Results

A total of 107 differentially expressed genes were identified through analysis between SSc patients and healthy controls. P4HA3 (α subunit of Collagen prolyl 4-hydroxylases, C-P4Hs) was identified by PPI network analysis. P4HA3 was the sole upregulated gene and positively correlated with the modified Rodnan skin score. PI3K/AKT signaling pathway was enriched by GSEA for single-gene to obtain P4HA3-related pathways. Single-cell analysis detected predominant TGF-β1 upregulation in immune cells, particularly in CD14⁺CD16⁻ monocytes, and P4HA3 showed elevated expression in SFRP2^high fibroblasts. Immunohistochemistry indicated that P4HA3- and TGF-β1-positive cell numbers were elevated in the dermal layers of SSc patients. P4HA3 was also elevated in bleomycin-treated mice and TGF-β1-induced human fibroblasts. Inhibition of C-P4Hs ameliorated experimental fibrosis in bleomycin-treated mice and TGF-β1-induced human fibroblasts. Hydroxyproline levels were reduced following P4HA3 knockdown in human fibroblasts.

Conclusion

Our results suggest that P4HA3 is upregulated by TGF-β1 secreted from immune cells to promote collagen synthesis in SSc. Inhibition of C-P4Hs is a potential therapeutic approach for SSc fibrosis.

目的系统性硬化症（SSc）是一种复杂的自身免疫性疾病，导致皮肤和内脏器官纤维化。尽管治疗取得了进展，但由于器官纤维化，SSc的死亡率很高。本研究旨在确定一种治疗SSc的潜在抗纤维化疗法。方法sssc生物信息学数据（GSE181549和GSE138669）从公共基因表达Omnibus （GEO）数据库中获取。随后，我们进行了差异分析、蛋白-蛋白相互作用（Protein-protein interaction， PPI）网络构建、基因富集分析，鉴定出一个关键的纤维化基因，并进行验证。结果通过分析SSc患者与健康对照共鉴定出107个差异表达基因。P4HA3（胶原脯氨酸4-羟化酶的α亚基，C-P4Hs）通过PPI网络分析得到。P4HA3是唯一上调的基因，与改良罗德曼皮肤评分呈正相关。通过GSEA对PI3K/AKT信号通路进行单基因富集，获得p4ha3相关通路。单细胞分析检测到免疫细胞中TGF-β1的显著上调，特别是在CD14+CD16−单核细胞中，P4HA3在sfrp2高的成纤维细胞中表达升高。免疫组化结果显示，SSc患者真皮中P4HA3-和TGF-β1阳性细胞数量升高。P4HA3在博莱霉素处理小鼠和TGF-β1诱导的人成纤维细胞中也升高。抑制C-P4Hs可改善博莱霉素处理小鼠和TGF-β1诱导的人成纤维细胞的实验性纤维化。在人成纤维细胞中，P4HA3敲除后羟脯氨酸水平降低。结论免疫细胞分泌的TGF-β1上调P4HA3，促进SSc胶原合成。抑制C-P4Hs是SSc纤维化的一种潜在治疗方法。

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引用次数: 0

Cre-driven tdTomato expression unexpectedly confers resistance to peripheral but not central lupus in dLckCre mice 基因驱动的tdTomato表达意外地赋予dckcre小鼠外周性狼疮而非中枢性狼疮的抗性

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-09-30 DOI: 10.1016/j.jtauto.2025.100320

Ning Han , Keer Wang , Dan Yang , Mingxuan Han, Xiaoxiao Hou, Zhenghao Xu

The Cre-driven tdTomato reporter system is widely used to visualize gene expression and cellular dynamics. Here we tested the impact of the tdTomato reporter system on the progression of both central and peripheral manifestations of systemic lupus erythematosus (SLE) in dLckCre mice. We crossed dLckCre mice with ROSA26^floxed^{^-}^{Stop-tdTomato} mice to generate conditional dLck-driven tdTomato reporter mice (DT mice). Then, SLE models were induced by pristane injection in DT mice or by crossing DT mice with B6/lpr mice. Central and peripheral manifestations of SLE were assessed. Surprisingly, we found that DT mice exhibited a significant reduction in the progression of peripheral manifestations of SLE, evidenced by decreased severity of lymph node and splenic lesions, and improved renal pathology. However, DT mice showed similar central manifestations of SLE as control mice, evidenced by similar behavioral performance, CD4⁺ T cell infiltration in the choroid plexus, and microglial activation in the hippocampus. Flow cytometry revealed a significant reduction in the proportion of double-negative (DN) T cells in the peripheral blood of DT mice. Immunofluorescence analysis confirmed no significant differences in microglial morphology or choroid plexus CD4⁺ T cell infiltration between DT lupus mice and control mice. Notably, over 80 % of the infiltrating lymphocytes in the choroid plexus of lupus mice were CD4⁺ T cells. Adoptive transfer experiments further confirmed that these ectopically aggregated CD4⁺ T cells in the choroid plexus constitute a key pathogenic factor driving the onset and progression of neuropsychiatric SLE (NPSLE). Thus, conditional tdTomato expression alleviated peripheral but not central manifestations of SLE in dLckCre mice, suggesting a diverse role of dLck-labeled T lymphocytes in SLE development. Our results also provide additional evidence supporting the existence of a distinct separation mechanism between peripheral and central manifestations of SLE.

cred驱动的tdTomato报告系统被广泛用于基因表达和细胞动力学的可视化。在这里，我们测试了tdTomato报告系统对dckcre小鼠系统性红斑狼疮（SLE）中枢和外周表现进展的影响。我们将dckcre小鼠与ROSA26floxed-Stop-tdTomato小鼠杂交，生成条件dlck驱动的tdTomato报告小鼠（DT小鼠）。然后，用普里stane注射DT小鼠或将DT小鼠与B6/lpr小鼠杂交诱导SLE模型。评估SLE的中枢和外周表现。令人惊讶的是，我们发现DT小鼠在SLE周围表现的进展中表现出显著的减少，淋巴结和脾脏病变的严重程度降低，肾脏病理改善。然而，DT小鼠表现出与对照小鼠相似的SLE中枢表现，表现为相似的行为表现、脉络膜丛CD4+ T细胞浸润和海马小胶质细胞活化。流式细胞术显示，DT小鼠外周血中双阴性（DN） T细胞的比例显著降低。免疫荧光分析证实，DT狼疮小鼠与对照组小胶质细胞形态及脉络膜丛CD4+ T细胞浸润无显著差异。值得注意的是，狼疮小鼠脉络膜丛浸润淋巴细胞中超过80%是CD4+ T细胞。过继性转移实验进一步证实，脉络膜丛中这些异位聚集的CD4+ T细胞是驱动神经精神性SLE （NPSLE）发生和发展的关键致病因素。因此，条件tdTomato表达减轻了dclcre小鼠SLE的外周表现，而不是中枢表现，提示dclk标记T淋巴细胞在SLE发展中的多种作用。我们的研究结果还提供了额外的证据，支持SLE外周和中枢表现之间存在明显的分离机制。

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引用次数: 0

Vitamin D3 encapsulated in polymeric nanoparticles to dampen the pro-inflammatory immune response 维生素D3封装在聚合纳米颗粒中，以抑制促炎免疫反应

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-09-30 DOI: 10.1016/j.jtauto.2025.100321

Julia Minnee , Jorge Cuenca-Escalona , Johanna Bödder , Georgina Flórez-Grau , Esther C. de Jong , I. Jolanda M. de Vries

1α25-dihydroxyvitamin D3, the active metabolite of vitamin D3 (VD3), is a modulator of inflammation well-known for its ability to promote anti-inflammatory and tolerogenic immune responses. It is therefore an attractive agent for the attenuation of inflammatory responses and the development of tolerogenic immunity in autoimmune diseases. To overcome VD3 toxicity and enhance its in vivo performance, nanoparticles (NPs) have emerged as a promising delivery platform. Therefore, in this study, we have developed VD3-loaded polymeric nanoparticles (VD3-NPs) as a therapeutical strategy for the treatment of autoimmune disorders. We demonstrate that VD3-NPs could successfully be generated and that they significantly inhibit secretion of IL-6, IL-10, IL-23, and TNFα in human whole blood cultures. We observed that poly(lactic-co-glycolic acid) (PLGA) NPs are efficiently taken up by neutrophils, monocytes and B cells, prompting further investigation into the effect of VD3-NPs on these subsets. Investigation into each of the immune cell subsets demonstrated that the VD3-NPs were able inhibit cytokine secretion by both monocytes and neutrophils. Moreover, VD3-NPs induced a tolerogenic phenotype in monocytes. In B cells, we observed that VD3-NPs impaired in vitro plasma B cell differentiation and suppressed antibody production. Together, our results validate for the first time in primary human cells the therapeutic potential of VD3 encapsulated in PLGA NPs, posing an attractive strategy for the treatment of autoimmune diseases.

1α25-二羟基维生素D3是维生素D3 （VD3）的活性代谢物，是一种炎症调节剂，以其促进抗炎和耐受性免疫反应的能力而闻名。因此，对于自身免疫性疾病的炎症反应的衰减和耐受性免疫的发展，它是一种有吸引力的药物。为了克服VD3的毒性并提高其在体内的性能，纳米颗粒（NPs）已成为一种有前途的给药平台。因此，在这项研究中，我们开发了装载vd3的聚合物纳米颗粒（VD3-NPs）作为治疗自身免疫性疾病的治疗策略。我们证明了VD3-NPs可以成功生成，并且它们可以显著抑制人全血培养中IL-6、IL-10、IL-23和tnf - α的分泌。我们观察到聚乳酸-羟基乙酸（PLGA） NPs被中性粒细胞、单核细胞和B细胞有效吸收，这促使我们进一步研究VD3-NPs对这些亚群的影响。对每个免疫细胞亚群的研究表明，VD3-NPs能够抑制单核细胞和中性粒细胞的细胞因子分泌。此外，VD3-NPs在单核细胞中诱导耐受性表型。在B细胞中，我们观察到VD3-NPs损害了体外血浆B细胞的分化并抑制了抗体的产生。总之，我们的研究结果首次在人类原代细胞中验证了包裹在PLGA NPs中的VD3的治疗潜力，为治疗自身免疫性疾病提出了一种有吸引力的策略。

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引用次数: 0

Integrative mass spectrometry-driven multi-omics and single cell technologies in ankylosing spondylitis: insights into pathogenesis, biomarker discovery, and precision medicine 强直性脊柱炎的综合质谱驱动的多组学和单细胞技术：发病机制、生物标志物发现和精准医学的见解

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-09-24 DOI: 10.1016/j.jtauto.2025.100319

Yan Gao , Xinge Li , Fengting Luo , Ruibing Chen , Xiangyang Zhang

Ankylosing spondylitis (AS), a chronic inflammatory arthritis primarily affecting the axial skeleton, presents significant clinical challenges due to its complex pathogenesis, delayed diagnosis, and heterogeneous therapeutic responses. This review highlights the pivotal role of mass spectrometry (MS)-based multi-omics technologies in elucidating AS pathogenesis, identifying disease-specific biomarkers, and advancing precision medicine for AS. The fundamental principles of MS are outlined, encompassing ionization methods like electrospray and matrix-assisted laser desorption/ionization, mass analyzers such as orbitrap and time-of-flight, and separation systems including liquid and gas chromatography. These technologies enable highly sensitive and comprehensive profiling of proteomes, metabolomes, and lipidomes. Proteomics analyses have revealed dysregulated pathways and identified key biomarkers, including complement components, matrix metalloproteinases and the panel “C-reactive protein + serum amyloid A1”, for distinguishing active AS from healthy controls and stable AS. Metabolomics studies emphasize disturbances in tryptophan-kynurenine metabolism and gut microbiome-derived metabolites, including short-chain fatty acids, thereby linking microbial imbalance to inflammatory responses. A combination of three metabolites (3-amino-2-piperidone, hypoxanthine, and octadecylamine) has shown promise as serum biomarkers for AS diagnosis. Lipidomics profiling reveals significant changes in phospholipid composition. Furthermore, emerging single cell technologies (e.g., mass cytometry) have dissected immune heterogeneity in AS, revealing chemokine signaling dysregulation in monocyte and T-cell subclusters. Persistent challenges and future advancements, such as data heterogeneity, cohort limitations, and the interpretability of artificial intelligence models for multi-omics integration were discussed. By integrating technological innovation with clinical insights, this review systematically summarizes multiple potential biomarker panels for AS, in which multi-omics-driven strategies facilitate early diagnosis, mechanistic subtyping, and personalized therapies, ultimately improving patient outcomes in AS.

强直性脊柱炎（AS）是一种主要影响中轴骨骼的慢性炎症性关节炎，由于其复杂的发病机制、延迟的诊断和异质性的治疗反应，给临床带来了重大挑战。本文综述了基于质谱（MS）的多组学技术在阐明AS发病机制、识别疾病特异性生物标志物和推进AS精准医学方面的关键作用。概述了质谱的基本原理，包括电离方法，如电喷雾和基质辅助激光解吸/电离，质量分析仪，如轨道阱和飞行时间，分离系统，包括液相和气相色谱。这些技术能够对蛋白质组、代谢组和脂质组进行高度敏感和全面的分析。蛋白质组学分析揭示了失调的途径，并确定了关键的生物标志物，包括补体成分、基质金属蛋白酶和“c反应蛋白+血清淀粉样蛋白A1”面板，用于区分活性AS与健康对照和稳定AS。代谢组学研究强调色氨酸-犬尿氨酸代谢和肠道微生物衍生代谢物（包括短链脂肪酸）的紊乱，从而将微生物失衡与炎症反应联系起来。三种代谢物（3-氨基-2-哌啶酮、次黄嘌呤和十八胺）的组合有望作为as诊断的血清生物标志物。脂质组学分析揭示了磷脂组成的显著变化。此外，新兴的单细胞技术（如大量细胞术）已经解剖了AS的免疫异质性，揭示了单核细胞和t细胞亚群中的趋化因子信号失调。讨论了持续的挑战和未来的进展，如数据异质性、队列限制和多组学集成人工智能模型的可解释性。通过将技术创新与临床见解相结合，本综述系统地总结了多个潜在的AS生物标志物面板，其中多组学驱动策略促进了AS的早期诊断，机制亚型和个性化治疗，最终改善了AS患者的预后。

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引用次数: 0

Clinical efficacy and immunomodulation of double-filtration plasmapheresis in autoimmune encephalitis: A prospective study highlighting the importance of timely initiation 双滤过血浆置换治疗自身免疫性脑炎的临床疗效和免疫调节作用：一项前瞻性研究，强调及时启动的重要性

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-09-23 DOI: 10.1016/j.jtauto.2025.100318

Hongyan Li , Kan Wang , Qiuju Li , Xuzhong Pei , Jie Ding , Jing Peng , Wanwan Li , Xiajun Zhou , Desheng Zhu , Yangtai Guan

Background and purpose

Double-filtration plasmapheresis (DFPP) has emerged as a plasma-saving alternative to therapeutic plasma exchange for autoimmune encephalitis (AE), but prospective evidence regarding its dual effects on both clinical efficacy and immunomodulation remains limited. This study aimed to evaluate the clinical and immunological effects of DFPP in AE.

Methods

In this prospective single-center cohort study, 57 patients diagnosed with AE according to international criteria were enrolled between 2018 and 2023. Participants received DFPP (median 3–5 sessions), either alone or combined with immunotherapies. The primary outcome was neurological improvement, measured by the change in modified Rankin Scale (ΔmRS). Secondary outcomes included symptomatic change (ΔCASE score), immunological parameter shifts, and adverse events. Subgroup analyses were conducted based on antibody type, treatment timing, and combination therapies.

Results

The cohort had a median age of 47 years (IQR: 24–65), with 49.1 % being female. DFPP significantly reduced median mRS scores from 3.00 to 1.00 (p < 0.001) and CASE scores from 3.00 to 1.00 (p < 0.001). The overall functional improvement rate was 71.9 %. Initiation of DFPP within 14 days of symptom onset was associated with significantly higher response rates (100 % vs. 63.6 %, p < 0.05) and greater neurological improvement (p < 0.05). Combination with IVMP or IVIG did not enhance efficacy compared to DFPP alone (p = 0.600). Immunological profiling revealed significant reductions in IgG (77.55 %), IgA (76.11 %), and IgM (79.96 %), along with modulation of lymphocyte subsets and cytokine levels. Adverse events occurred in 28.1 % of patients, predominantly mild catheter-related thrombosis.

Conclusions

DFPP is an effective and well-tolerated treatment for autoimmune encephalitis, significantly improving neurological function modulates immune responses.

背景和目的双滤过血浆置换术（DFPP）已成为治疗自身免疫性脑炎（AE）的一种血浆保存替代方法，但关于其临床疗效和免疫调节双重作用的前瞻性证据仍然有限。本研究旨在评价DFPP治疗AE的临床和免疫学效果。方法在这项前瞻性单中心队列研究中，纳入了2018年至2023年间57例根据国际标准诊断为AE的患者。参与者接受DFPP（中位3-5个疗程），单独或联合免疫疗法。主要结果是神经系统改善，通过修改Rankin量表（ΔmRS）的变化来衡量。次要结局包括症状改变（ΔCASE评分）、免疫参数变化和不良事件。根据抗体类型、治疗时间和联合治疗进行亚组分析。结果该队列患者中位年龄为47岁（IQR: 24-65），女性占49.1%。DFPP显著降低mRS评分中位数，从3.00降至1.00 (p < 0.001)， CASE评分从3.00降至1.00 （p < 0.001）。整体功能改善率为71.9%。症状出现后14天内开始DFPP治疗的有效率显著提高（100% vs. 63.6%, p < 0.05），神经系统改善显著（p < 0.05）。与单用DFPP相比，联合IVMP或IVIG没有提高疗效（p = 0.600）。免疫学分析显示IgG（77.55%）、IgA（76.11%）和IgM（79.96%）显著降低，淋巴细胞亚群和细胞因子水平也有调节。28.1%的患者发生不良事件，主要是轻度导管相关血栓形成。结论sdfpp治疗自身免疫性脑炎是一种有效且耐受性良好的治疗方法，可显著改善神经功能，调节免疫反应。

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引用次数: 0

Serum test for secretory component-containing anti-citrullinated protein antibodies as a novel prognostic tool in rheumatoid arthritis at-risk subjects 血清检测含有抗瓜氨酸化蛋白抗体的分泌成分作为类风湿关节炎危险受试者的一种新的预后工具

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-09-17 DOI: 10.1016/j.jtauto.2025.100317

Klara Martinsson , Simon Åhammar , Alexandra Cîrciumaru , Bence Réthi , Michael Ziegelasch , Aase Hensvold , Alf Kastbom

Individuals with autoantibodies against citrullinated proteins (ACPA) and musculoskeletal symptoms face increased risk of developing rheumatoid arthritis (RA). There are knowledge gaps concerning who will develop disease, and predictors of RA onset are highly warranted. A mucosal origin hypothesis in RA is gaining increasing support, for instance by a previous study showing that secretory component-containing ACPA (SC ACPA) in the circulation are prognostic for RA onset. This study aimed to confirm the prognostic value of serum SC ACPA in a large cohort of symptomatic at-risk subjects and to establish a cutoff level for the prognostic use of SC ACPA testing.

Baseline sera from an observational prospective cohort of IgG ACPA positive individuals with musculoskeletal complaints (Karolinska cohort, n = 266) were tested for SC ACPA by ELISA. SC ACPA levels were increased among subjects subsequently developing arthritis (n = 100, median 62 arbitrary units (AU)/mL) compared to those who did not (n = 166, median 40 AU/mL; p < 0.001). A cutoff level for the optimal discrimination concerning future arthritis onset was established by Youden's index, resulting in 81 subjects (30 %) testing positive for SC ACPA, whereof 45 (56 %) progressed to arthritis. Among those testing negative (n = 185), significantly fewer progressed (n = 55, 30 %; p < 0.001). This cutoff was then tested in the previously studied at-risk cohort (n = 82), revealing similar prognostic performance in both cohorts (sensitivity 45 % and 41 %; specificity 78 % and 81 %). We conclude that serum SC ACPA testing is of potential clinical value in symptomatic at-risk subjects and strengthens the mucosal association in RA development.

具有抗瓜氨酸化蛋白（ACPA）自身抗体和肌肉骨骼症状的个体患类风湿关节炎（RA）的风险增加。关于谁将会发展为疾病存在知识空白，而类风湿关节炎发病的预测因素是非常必要的。RA的粘膜起源假说正获得越来越多的支持，例如，先前的一项研究表明，循环中含有分泌成分ACPA （SC ACPA）是RA发病的预后因素。本研究旨在确认血清SC ACPA在一大群有症状的高危受试者中的预后价值，并建立SC ACPA检测用于预后的临界值。通过ELISA检测具有肌肉骨骼疾患的IgG ACPA阳性个体的基线血清（卡罗林斯卡队列，n = 266）。与未发生关节炎的受试者（n = 166，中位数40 AU/mL； p < 0.001）相比，随后发生关节炎的受试者SC ACPA水平升高（n = 100，中位数62任意单位(AU)/mL）。通过约登指数（Youden's index）建立了最佳鉴别未来关节炎发病的截止水平，结果81名受试者（30%）SC ACPA检测呈阳性，其中45名（56%）进展为关节炎。在检测呈阴性的患者（n = 185）中，进展明显较少（n = 55,30 %; p < 0.001）。然后在先前研究的高危队列（n = 82）中测试该截止值，结果显示两个队列的预后表现相似（敏感性为45%和41%；特异性为78%和81%）。我们得出结论，血清SC ACPA检测在有症状的高危受试者中具有潜在的临床价值，并加强了RA发展中的粘膜相关性。

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引用次数: 0

Immune responses to infection and autoimmune diseases in the UK biobank 英国生物银行对感染和自身免疫性疾病的免疫反应

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-09-17 DOI: 10.1016/j.jtauto.2025.100315

Choa Yun , Dongwon Yoon , Sun Young Jung , Moonsuk Kim , May A. Beydoun , Lenore Launer , Minkyo Song

Background

Infections may trigger autoimmunity, but large-scale studies on antibodies to infections and their associations with autoimmune diseases are limited. We aim to better understand the etiologic role of infection.

Methods

We analyzed 9429 UK Biobank participants for 45 antibody responses to 20 pathogens. Association between seropositivity and autoimmune diseases was assessed with logistic regression for prevalence and Cox regression for incidence, applying Bonferroni correction. 49 autoimmune diseases were ascertained via International Classification of Diseases codes and self-reported diagnoses, of which 14 were analyzed.

Results

At baseline, 671 (7.1 %, 58 % female) had at least one autoimmune disease. In males, HSV-1 seropositivity was linked to lower odds of rheumatic fever/rheumatic heart disease (odds ratio 0.29 [95 % CI 0.12–0.68]), at Bonferroni significance. At nominal significance (p < 0.05), eight associations were observed—positive: HHV-6B–type 1 diabetes, H. pylori–sarcoidosis, HPV-18–type 1 diabetes, JCV–psoriasis; inverse: T. gondii–celiac disease, H. pylori–Crohn’s disease, HSV-1–multiple sclerosis, HHV-7–rheumatoid arthritis. Of 8758 autoimmune disease-free individuals, 627 developed autoimmune diseases. In females, seropositivity to HPV-18 was associated with rheumatoid arthritis (hazard ratio 2.26 [95 % CI 1.34–3.82]), at Bonferroni significance. HRs for 3 nominal seropositivity/autoimmune disease associations (1 inverse, 2 positive) ranged from 0.42 [95 % CI 0.21–0.87] (HHV-6B/vasculitis) to 3.62 [95 % CI 1.29–10.12] (C. trachomatis/psoriasis) in both sexes.

Conclusions

This study examined cross-sectional and prospective associations between antibodies to infectious agents and autoimmune diseases. Inverse associations may suggest infections could train the immune system or reflect altered host immunity, while positive associations indicate potential autoimmune triggers. These findings enhance understanding of autoimmune disease etiology and provide a foundation for future mechanistic studies and hypothesis-driven research.

感染可能引发自身免疫，但对感染抗体及其与自身免疫性疾病的关联的大规模研究是有限的。我们的目标是更好地了解感染的病因学作用。方法对9429名UK Biobank参与者进行20种病原菌45种抗体应答分析。血清阳性与自身免疫性疾病之间的关系采用流行率的logistic回归和发生率的Cox回归进行评估，并应用Bonferroni校正。通过国际疾病分类代码和自我报告诊断确定了49种自身免疫性疾病，并对其中14种进行了分析。结果基线时，671例（7.1%，58%为女性）至少有一种自身免疫性疾病。在男性中，HSV-1血清阳性与风湿热/风湿性心脏病的发生率较低相关（优势比0.29 [95% CI 0.12-0.68]），具有Bonferroni显著性。在名义意义上（p < 0.05）， 8个相关性观察到阳性：hhv - 6b型1型糖尿病，幽门螺杆菌结节病，hpv -18型1型糖尿病，jcv -牛皮癣；逆：弓形虫-乳糜泻，幽门螺杆菌-克罗恩病，单纯疱疹病毒-1多发性硬化，单纯疱疹病毒-7类风湿性关节炎。在8758名无自身免疫性疾病的个体中，627人患上了自身免疫性疾病。在女性中，HPV-18血清阳性与类风湿关节炎相关（危险比2.26 [95% CI 1.34-3.82]），具有Bonferroni显著性。3种名义血清阳性/自身免疫性疾病相关（1例阴性，2例阳性）的hr在两性中范围从0.42 [95% CI 0.21-0.87] （HHV-6B/血管炎）到3.62 [95% CI 1.29-10.12]（沙眼衣原体/牛皮癣）。结论：本研究探讨了传染性病原体抗体与自身免疫性疾病之间的横断面和前瞻性关联。负相关可能表明感染可能训练免疫系统或反映宿主免疫改变，而正相关表明潜在的自身免疫触发因素。这些发现增强了对自身免疫性疾病病因学的理解，并为未来的机制研究和假设驱动的研究提供了基础。

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引用次数: 0

Short-chain fatty acids from gut microbiota restore Th17/Treg balance in rheumatoid arthritis: Mechanisms and therapeutic potential 来自肠道菌群的短链脂肪酸恢复类风湿关节炎Th17/Treg平衡：机制和治疗潜力

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-09-16 DOI: 10.1016/j.jtauto.2025.100316

Aimei Pang , Shuangshuang Pu , Yinghui Pan , Ning Huang , Dake Li

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and joint destruction. Dysregulation of the Th17/Treg balance is a key immunological hallmark of RA. Emerging evidence highlights the critical role of gut microbiota-derived short-chain fatty acids (SCFAs) in maintaining immune homeostasis. This review systematically elucidates how SCFAs modulate the Th17/Treg equilibrium through three synergistic mechanisms: (1) metabolic reprogramming via AMPK/mTOR signaling, (2) epigenetic regulation by inhibiting HDAC, and (3) modulation of cytokine cascades. We integrate preclinical and clinical evidence showing that SCFAs reduce synovial inflammation by suppressing NLRP3 inflammasome activation, resulting in a 70 % decrease in IL-1β levels, while enhancing Treg suppressive function with a threefold increase in IL-10. Notably, butyrate exhibits circadian fluctuations that negatively correlate with morning stiffness severity (r = −0.82, p < 0.01), suggesting novel chronotherapeutic opportunities. Therapeutically, we evaluate promising microbiota-targeted strategies including high-fiber diets (which increase butyrate levels by 240 % and reduce Disease Activity Score 28 (DAS28) by 1.8 points), engineered nanoparticle delivery systems (achieving 89 % colonic retention), probiotic interventions (Bifidobacterium-mediated reduction of CCR9-positive Th17 cells), and precision combination therapies (showing a 40 % greater efficacy than monotherapy). Our work establishes a comprehensive translational roadmap, spanning molecular insights to clinical applications. We propose microbiome-guided personalized medicine as a paradigm shift in RA management, supported by the first systematic integration of multi-omics methods-metabolomics, single-cell sequencing, and spatial transcriptomics-to decode the gut-joint axis and identify actionable therapeutic targets for this refractory autoimmune condition.

类风湿性关节炎（RA）是一种以滑膜炎症和关节破坏为特征的慢性自身免疫性疾病。Th17/Treg平衡失调是RA的关键免疫学标志。新出现的证据强调了肠道微生物来源的短链脂肪酸（SCFAs）在维持免疫稳态中的关键作用。本综述系统阐述了SCFAs如何通过三种协同机制调节Th17/Treg平衡：(1)通过AMPK/mTOR信号通路进行代谢重编程，(2)通过抑制HDAC进行表观遗传调控，以及(3)调节细胞因子级联反应。我们综合临床前和临床证据表明，SCFAs通过抑制NLRP3炎性体激活来减少滑膜炎症，导致IL-1β水平降低70%，同时通过将IL-10增加三倍来增强Treg抑制功能。值得注意的是，丁酸盐表现出昼夜节律波动与晨僵严重程度负相关（r = - 0.82, p < 0.01），这表明有新的时间治疗机会。在治疗方面，我们评估了有希望的针对微生物群的策略，包括高纤维饮食（将丁酸盐水平提高240%，将疾病活动评分28 （DAS28）降低1.8分），工程纳米颗粒递送系统（实现89%的结肠保留），益生菌干预（双歧杆菌介导的ccr9阳性Th17细胞减少），以及精确的联合治疗（显示比单一治疗效率高40%）。我们的工作建立了一个全面的转化路线图，跨越分子的见解到临床应用。我们提出以微生物组为指导的个体化医学作为RA管理的范式转变，在多组学方法（代谢组学、单细胞测序和空间转录组学）的首次系统整合的支持下，解码肠道关节轴并确定这种难治性自身免疫性疾病的可行治疗靶点。

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引用次数: 0