Autoimmunity reviews最新文献_第6页

Systemic sclerosis and AHR: Shedding light on a hidden connections 系统性硬化和AHR：揭示隐藏的联系

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-20 DOI: 10.1016/j.autrev.2025.103915

Anna Wajda , Agnieszka Paradowska-Gorycka , Charlotte Esser

Systemic sclerosis (SSc) is a complex and debilitating autoimmune disease marked by fibrosis of the skin and inner organs, alongside chronic inflammation, and vascular abnormalities. SSc pathogenesis involves both genetic and environmental factors, such as silica dust or benzene exposure but the underlying molecular mechanisms regulating fibrogenesis and organ involvement are not fully understood. In part due to this knowledge gap, treatment options are limited. In this review we look at the possible role of the aryl hydrocarbon receptor (AHR), a transcription factor involved in immunomodulation, fibrosis and drug metabolism and inflammatory responses, especially in barrier organs. AHR activation by binding to one of its many small molecular weight ligands can result in gene-expression changes in the nucleus (its role as a transcription factor) but also lead to knock-on effects on other signaling pathways via direct binding (e.g., to NFkB) or via AHR's protein degradation capacity (E3 ligase). In some cell types transcription target genes include the fibrogenic cytokine TGF-β or metalloproteinases responsible for extracellular matrix remodeling. AHR has been shown to be highly expressed in all cutaneous cell populations, and to be critical for skin homeostasis. Given its context-dependent effects, AHR may act as both a pro- and anti-fibrotic regulator in SSc, depending on ligand availability and cellular environment. This dual role highlights AHR as a potential therapeutic target, where selective agonists or antagonists could help restore immune and fibrotic homeostasis. Here, we explore these mechanisms and discuss the potential of AHR as a therapeutic target for modulating disease progression and improving patient outcomes.

系统性硬化症（SSc）是一种复杂的、使人衰弱的自身免疫性疾病，其特征是皮肤和内脏纤维化，同时伴有慢性炎症和血管异常。SSc的发病机制涉及遗传和环境因素，如二氧化硅粉尘或苯暴露，但调节纤维发生和器官受损伤的潜在分子机制尚不完全清楚。部分由于这种知识差距，治疗选择是有限的。在这篇综述中，我们着眼于芳烃受体（AHR）的可能作用，芳烃受体是一种转录因子，参与免疫调节、纤维化、药物代谢和炎症反应，特别是在屏障器官中。AHR通过与其众多小分子量配体中的一种结合而激活，可导致细胞核中基因表达的变化（其作为转录因子的作用），但也会通过直接结合（例如，与NFkB）或通过AHR的蛋白质降解能力（E3连接酶）对其他信号通路产生连锁反应。在某些细胞类型中，转录靶基因包括纤维化细胞因子TGF-β或负责细胞外基质重塑的金属蛋白酶。AHR已被证明在所有皮肤细胞群中高度表达，并且对皮肤稳态至关重要。鉴于其上下文依赖效应，AHR可能在SSc中作为促纤维化和抗纤维化调节剂，这取决于配体的可用性和细胞环境。这种双重作用突出了AHR作为潜在的治疗靶点，选择性激动剂或拮抗剂可以帮助恢复免疫和纤维化的稳态。在这里，我们探讨了这些机制，并讨论了AHR作为调节疾病进展和改善患者预后的治疗靶点的潜力。

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引用次数: 0

In search of biomarkers for prediction of drug treatment responses in rheumatoid arthritis: Lessons learned and future perspectives 寻找类风湿性关节炎药物治疗反应预测的生物标志物：经验教训和未来展望

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-20 DOI: 10.1016/j.autrev.2025.103914

Athanasia Dara, Nikolaos I. Vlachogiannis, George E. Fragoulis, Maria G. Tektonidou, Petros P. Sfikakis

Prompt initiation of effective drug treatment is crucial for controlling inflammation and preventing disease progression in rheumatoid arthritis, the most prevalent systemic rheumatic disease. The growing range of drug therapies over the past three decades and the fact that only a minority of patients achieve sustained long-term remission with any given therapy, make imperative the need for biomarkers predicting responses to specific drugs. Moreover, promising therapeutic approaches under development, namely cellular therapies, could be promptly applicable at earlier disease stages in about 10-15 % of RA patients who will be refractory to all approved drugs. In this scoping review of original articles published until 25th of July 2025, we present a critical overview of the literature pertaining to the prognostic value of blood immunophenotyping, circulating proteins and blood proteomics, transcriptomics, metabolomics and lipidomics, as well as of endogenous cortisol production and synovial histopathology. We also discuss the emerging use of artificial intelligence-based approaches for developing response prediction models that integrate clinical features with molecular profiling. We conclude that current knowledge does not allow to discern future responders to methotrexate and/or to different biologic agents from non-responders because established biomarkers to identify those patients who will benefit the most from each therapeutic option are lacking. We also emphasize the lack of standardized research approaches to discover biomarkers predicting drug treatment responses and try to identify the relevant pitfalls and describe the lessons learned over the years. Finally, we propose a roadmap and the application of advanced analytical and machine learning techniques for future research in this area.

类风湿性关节炎是最普遍的系统性风湿性疾病，及时开始有效的药物治疗对于控制炎症和预防疾病进展至关重要。在过去的三十年中，药物治疗的范围不断扩大，而且只有少数患者通过任何给定的治疗获得持续的长期缓解，这使得对生物标志物预测特定药物反应的需求势在必行。此外，正在开发的有希望的治疗方法，即细胞疗法，可以迅速应用于大约10- 15%的RA患者的早期疾病阶段，这些患者对所有批准的药物都是难治性的。在这篇截至2025年7月25日发表的原创文章的范围综述中，我们提出了关于血液免疫表型、循环蛋白和血液蛋白质组学、转录组学、代谢组学和脂质组学以及内源性皮质醇产生和滑膜组织病理学的预后价值的文献综述。我们还讨论了基于人工智能的方法的新兴应用，用于开发将临床特征与分子谱相结合的反应预测模型。我们得出的结论是，目前的知识无法区分未来对甲氨蝶呤和/或不同生物制剂的反应者和无反应者，因为缺乏确定将从每种治疗方案中获益最多的患者的既定生物标志物。我们还强调缺乏标准化的研究方法来发现预测药物治疗反应的生物标志物，并试图确定相关的陷阱，并描述多年来吸取的教训。最后，我们为该领域的未来研究提出了路线图和先进的分析和机器学习技术的应用。

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引用次数: 0

Rapid radiographic progression in rheumatoid arthritis: Definition, prediction and treatment 类风湿关节炎的快速影像学进展：定义、预测和治疗。

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-18 DOI: 10.1016/j.autrev.2025.103913

Bo Lv , Fanshu Li , Fanlei Hu , Liling Xu

Rapid radiographic progression (RRP) in rheumatoid arthritis (RA) is strongly correlated with unfavorable long-term prognostic outcomes. Early identification of RRP is paramount, as prompt intervention and the implementation of intensified therapeutic regimens have the potential to substantially improve clinical outcomes. This review summarized the different definitions and current key predictors of RRP, such as genetic predispositions, body mass index and so on. Furthermore, the existing matrix-based predictive models for RRP were compared. In addition, the potential treatment options for patients with RRP were also outlined. The objective of this review is to improve the early detection of RRP, thereby facilitating timely intervention and the adoption of personalized treatment paradigms that optimize patient prognosis.

类风湿关节炎（RA）的放射学快速进展（RRP）与不良的长期预后密切相关。早期识别RRP是至关重要的，因为及时干预和强化治疗方案的实施有可能大大改善临床结果。本文综述了RRP的不同定义和目前的主要预测因素，如遗传易感性、体重指数等。并对现有的基于矩阵的RRP预测模型进行了比较。此外，还概述了RRP患者的潜在治疗方案。本综述的目的是提高RRP的早期发现，从而促进及时干预和采用个性化治疗模式，优化患者预后。

引用次数: 0

Systemic lupus erythematosus in critical care: A systematic review of ICU outcomes and management 重症监护中的系统性红斑狼疮：ICU结局和管理的系统回顾。

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-17 DOI: 10.1016/j.autrev.2025.103911

Edith Ramírez-Lara , Claudia Mendoza-Pinto , Pamela Munguía-Realpozo , Miguel Ángel Saavedra-Salinas , Ivet Etchegaray-Morales , Jorge Ayón-Aguilar , Álvaro José Montiel-Jarquín , Socorro Martínez-Méndez

Background

Systemic lupus erythematosus (SLE) often progresses to critical illness requiring intensive care unit (ICU) admission, yet contemporary data on outcomes, prognostic factors, and therapeutic approaches are scattered.

Objective

To synthesize recent evidence on causes of ICU admission, mortality predictors, and management strategies in adult SLE.

Methods

A PRISMA-compliant search of PubMed, Web of Science and Cochrane Library (inception–31 December 2024) retrieved studies enrolling adults (≥18 years) with confirmed SLE treated in ICUs. Two reviewers independently selected articles and extracted data; methodological heterogeneity precluded meta-analysis, so results were narratively synthesized.

Results

Thirty-nine studies met the criteria. Infection (40 %), pulmonary involvement (17 %) and renal flares (13 %) were the most common admission triggers. Reported ICU mortality ranged from 20 % to 82 % but rose sharply when baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) exceeded 16, approximating 80 % mortality (sensitivity 84 %, specificity 90 %) and outperforming Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) in discriminating survivors. Additional independent predictors were APACHE II > 16, need for mechanical ventilation, renal replacement therapy and vasopressor support. Mechanical ventilation (59 %) and vasoactive agents (39 %) were the predominant ICU interventions. Immunomodulatory management was heterogeneous: high-dose corticosteroids and cyclophosphamide were ubiquitous, whereas mycophenolate, antimalarials, intravenous immunoglobulin, plasmapheresis, and extracorporeal membrane oxygenation were reserved for selected scenarios.

Conclusions

Early recognition of poor prognostic factors and prompt ICU admission are essential to improving outcomes in SLE.

背景：系统性红斑狼疮（SLE）经常发展为需要重症监护病房（ICU）住院的危重疾病，但目前关于结果、预后因素和治疗方法的数据分散。目的：综合有关成人SLE住院原因、死亡率预测因素和治疗策略的最新证据。方法：检索PubMed、Web of Science和Cochrane Library（开始- 2024年12月31日）的符合prisma标准的研究，检索了在icu中确诊SLE的成人（≥18 岁）。两位审稿人独立选择文章和提取数据；方法学异质性排除了meta分析，因此结果是叙述性综合的。结果：39项研究符合标准。感染（40 %）、肺部受累（17 %）和肾脏耀斑（13 %）是最常见的入院诱因。报告的ICU死亡率范围为20 %至82 %，但当基线系统性红斑狼疮疾病活动指数2000 （sledai2 K）超过16时，死亡率急剧上升，接近80 %（敏感性84 %，特异性90 %），在区分幸存者方面优于急性生理和慢性健康评估（APACHE） II和顺序器官衰竭评估（SOFA）。其他独立预测因子为APACHE II > 16、需要机械通气、肾脏替代治疗和血管加压药物支持。机械通气（59 %）和血管活性药物（39 %）是ICU的主要干预措施。免疫调节管理是异质性的：大剂量皮质类固醇和环磷酰胺普遍存在，而霉酚酸盐、抗疟药、静脉免疫球蛋白、血浆置换和体外膜氧合则保留用于特定情况。结论：早期识别不良预后因素并及时进入ICU治疗对于改善SLE预后至关重要。

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引用次数: 0

Gut microbiota in rheumatoid arthritis: Mechanistic insights, clinical biomarkers, and translational perspectives 类风湿关节炎的肠道微生物群：机制见解、临床生物标志物和翻译观点。

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-16 DOI: 10.1016/j.autrev.2025.103912

Xiang-Yu Qi , Meng-Xia Liu , Xiao-Jing Jiang , Tian Gao , Guo-Qiang Xu , He-Yi Zhang , Qin-Yi Su , Yi Du , Jing Luo , Sheng-Xiao Zhang

Rheumatoid arthritis (RA) is a systemic autoimmune disease shaped by complex interactions between genetics and environmental factors, among which gut microbiota has emerged as a critical modulator. Recent advances have implicated gut microbiota dysbiosis in RA pathophysiology, with evidence spanning mechanistic, diagnostic, and therapeutic dimensions. This review summarizes current knowledge of the gut-joint axis and outlines microbiota-based strategies for RA management. Numerous studies have demonstrated consistent alterations in gut microbial communities in patients with RA, with enrichment of Prevotella copri observed in 75% of patients with new-onset RA compared to 21.4% of healthy controls, suggesting a potential association with disease initiation. Mechanistically, we detail how microbial dysbiosis, including that of bacteria, fungi, and viruses, disrupts intestinal barrier integrity, skews T helper 17/T regulatory and T follicular helper/T follicular regulatory immune axes, induces molecular mimicry, and alters the profiles of microbial metabolites such as short-chain fatty acids. Diagnostically, microbial taxa and metabolites serve as promising biomarkers. Machine learning models based on microbiota profiles have achieved area under the curve (AUC) values exceeding 0.88, with discriminatory taxa such as Ruminococcus gnavus and Fusicatenibacter. Therapeutically, we reviewed microbiota-targeted interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, diet, and herbal medicines, highlighting the emerging field of pharmacomicrobiomics. Gut microbial signatures have shown promise in predicting treatment responses, including methotrexate efficacy via the enterotype-based gut microbial human index model (AUC = 0.945). This review proposes an integrated framework linking microbial alterations with RA onset and progression and presents gut microbiota as a promising frontier for biomarker discovery, personalized intervention, and precision medicine.

类风湿性关节炎（RA）是一种由遗传和环境因素复杂相互作用形成的系统性自身免疫性疾病，其中肠道菌群已成为重要的调节因子。最近的进展表明，肠道微生物群失调与类风湿性关节炎的病理生理有关，证据涵盖了机制、诊断和治疗方面。这篇综述总结了目前关于肠关节轴的知识，并概述了基于微生物群的RA管理策略。大量研究表明，RA患者的肠道微生物群落发生了一致的变化，75%的新发RA患者中观察到copri普雷沃氏菌的富集，而健康对照组中这一比例为21.4%，这表明与疾病发生有潜在的关联。在机制上，我们详细介绍了微生物生态失调，包括细菌、真菌和病毒，如何破坏肠道屏障完整性，扭曲T辅助17/T调节和T滤泡辅助/T滤泡调节免疫轴，诱导分子模仿，并改变微生物代谢物（如短链脂肪酸）的特征。在诊断方面，微生物分类群和代谢物是很有前途的生物标志物。基于微生物群剖面的机器学习模型已经实现了曲线下面积（AUC）值超过0.88，其中包括Ruminococcus gnavus和Fusicatenibacter等歧视性分类群。在治疗方面，我们回顾了针对微生物群的干预措施，如益生菌、益生元、抗生素、粪便微生物群移植、饮食和草药，重点介绍了药物微生物学的新兴领域。肠道微生物特征在预测治疗反应方面显示出前景，包括通过基于肠道类型的肠道微生物人类指数模型（AUC = 0.945）预测甲氨蝶呤的疗效。这篇综述提出了一个将微生物改变与RA的发病和进展联系起来的综合框架，并将肠道微生物群作为生物标志物发现、个性化干预和精准医学的一个有前途的前沿。

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引用次数: 0

The role of mTOR signaling pathway in systemic lupus erythematosus and systemic vasculitis mTOR信号通路在系统性红斑狼疮和系统性血管炎中的作用

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-12 DOI: 10.1016/j.autrev.2025.103910

Despina Michailidou , Yevgeniya Gartshteyn , Anca D. Askanase , Andras Perl

The mechanistic target of rapamycin (mTOR) is a central regulator of cellular proliferation, metabolism, survival and growth. The mTOR pathway consists of two protein complexes, mTORC1 and mTORC2, which have different sensitivities to rapamycin and cellular functions. mTOR regulates autophagy as well as the function and/or differentiation of many immune cells, including T cells, dendritic cells, natural killer cells, macrophages, neutrophils, and B cells. mTOR signaling is implicated in the pathogenesis of cancer, diabetes and several autoimmune diseases. In this review, we summarize how mTOR pathway may contribute to the pathogenesis of systemic lupus erythematosus (SLE) and systemic vasculitis. In SLE, mTOR activation induces activation of CD4 + T cells, skews differentiation towards Th17 cells resulting in Th17/Treg imbalance, increases production of IL-4 in CD4 − CD8− double-negative (DN) T cells, reduces the number of circulating CD8⁺ memory T cells, promotes B-cell proliferation, increases production of plasmacytes and secretion of autoantibodies, as well as activation of myeloid dendritic cells. In large vessel vasculitis, mTOR overactivity promotes endothelial cell growth, T cell differentiation towards Th1 and Th17 polarization, impairment of Tregs and activation of smooth muscle cell-derived myofibroblasts that contribute to arterial stenosis and ischemia, whereas in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, reduced activity of the mTOR signaling pathway is observed in neutrophils isolated during the active phase of the disease. Targeting mTOR pathway with rapamycin, rapalogues, or other mTOR inhibitors could be efficacious in the treatment of these complex autoimmune diseases.

雷帕霉素（mTOR）的机制靶点是细胞增殖、代谢、生存和生长的中心调节剂。mTOR通路由mTORC1和mTORC2两种蛋白复合物组成，它们对雷帕霉素的敏感性和细胞功能不同。mTOR调节自噬以及许多免疫细胞的功能和/或分化，包括T细胞、树突状细胞、自然杀伤细胞、巨噬细胞、中性粒细胞和B细胞。mTOR信号与癌症、糖尿病和几种自身免疫性疾病的发病机制有关。本文就mTOR通路在系统性红斑狼疮（SLE）和系统性血管炎发病机制中的作用进行综述。在SLE中，mTOR激活诱导CD4 + T细胞激活，向Th17细胞分化导致Th17/Treg失衡，增加CD4 - CD8 -双阴性（DN） T细胞中IL-4的产生，减少循环CD8+记忆T细胞的数量，促进b细胞增殖，增加浆细胞的产生和自身抗体的分泌，以及骨髓树突状细胞的激活。在大血管炎中，mTOR过度活性促进内皮细胞生长、T细胞向Th1和Th17极化分化、Tregs损伤和平滑肌细胞源性肌成纤维细胞的激活，从而导致动脉狭窄和缺血，而在抗中性粒细胞胞浆自身抗体（ANCA）相关血管炎中，在疾病活动期分离的中性粒细胞中观察到mTOR信号通路活性降低。用雷帕霉素、雷帕衍生物或其他mTOR抑制剂靶向mTOR通路可能有效治疗这些复杂的自身免疫性疾病。

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引用次数: 0

Unmet needs and emerging pharmacotherapies for autoimmune connective tissue disease-associated interstitial lung diseases 自身免疫性结缔组织病相关间质性肺疾病的未满足需求和新兴药物疗法

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-05 DOI: 10.1016/j.autrev.2025.103900

Yasuhiro Kondoh , Takao Fujii , Yoshikazu Inoue , Tatsuya Atsumi

Autoimmune connective tissue disease associated with interstitial lung disease (CTD-ILD) includes rheumatoid arthritis-associated ILD, systemic sclerosis-associated-ILD, and several other ILDs. Many patients with CTD-ILD—as well as individuals with other ILDs—develop a progressive pulmonary fibrosis (PPF) similar to idiopathic pulmonary fibrosis (IPF). PPF is characterized by worsening respiratory symptoms, declining lung function despite current pharmacotherapies, and ultimately early death. Current pharmacotherapies for CTD-ILD and PPF include glucocorticoids, immunosuppressants, and anti-fibrotic agents. Due to the scarcity of randomized clinical trials for CTD-ILD, many pharmacotherapies are generally administered off-label (although several are approved in Japan), with notable exceptions including nintedanib, an anti-fibrotic agent approved for SSc-ILD and chronic progressive fibrosing ILD in several countries. As the available agents only slow the decline of pulmonary function and are associated with treatment-limiting side effects, there is a need for more efficacious and tolerable pharmacotherapies for CTD-ILD and PPF. Promising compounds in clinical trials include nerandomilast (a preferential phosphodiesterase 4B inhibitor), admilparant (a lysophosphatidic acid receptor 1 antagonist), and inhaled treprostinil (a prostacyclin analogue). Nerandomilast may have both anti-fibrotic and immunomodulatory properties; in preclinical models of PPF, it reduced neutrophils and macrophages and down-regulated pro-fibrotic signaling pathways. Hopefully, therefore, this pipeline will produce new medications to ease the collectively large burden of CTD-ILD and PPF.

与间质性肺疾病相关的自身免疫性结缔组织疾病（CTD-ILD）包括类风湿关节炎相关的间质性肺疾病、系统性硬化症相关的间质性肺疾病和其他一些间质性肺疾病。许多患有ctd - ild的患者以及患有其他ild的个体发展为类似特发性肺纤维化（IPF）的进行性肺纤维化（PPF）。PPF的特点是呼吸系统症状恶化，尽管目前的药物治疗，肺功能下降，最终早期死亡。目前治疗CTD-ILD和PPF的药物包括糖皮质激素、免疫抑制剂和抗纤维化药物。由于缺乏CTD-ILD的随机临床试验，许多药物治疗通常是在标签外给药（尽管有几种在日本被批准），值得注意的例外包括nintedanib，一种抗纤维化药物，在几个国家被批准用于SSc-ILD和慢性进行性纤维化ILD。由于现有的药物只能减缓肺功能的下降，并伴有限制治疗的副作用，因此需要更有效和可耐受的药物治疗CTD-ILD和PPF。在临床试验中有前景的化合物包括nerandomilast（一种优先的磷酸二酯酶4B抑制剂）、admilparant（溶血磷脂酸受体1拮抗剂）和吸入性treprostiil（前列环素类似物）。尼兰多司特可能同时具有抗纤维化和免疫调节特性；在临床前PPF模型中，它减少了中性粒细胞和巨噬细胞，下调了促纤维化信号通路。因此，有希望的是，这一管道将产生新的药物，以减轻CTD-ILD和PPF的巨大负担。

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引用次数: 0

STING-inflammasome axis in autoimmune diseases and inflammation-related disease 自身免疫性疾病和炎症相关疾病的sting -炎性体轴

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-05 DOI: 10.1016/j.autrev.2025.103898

Shengjun Chai , Haiming Xu , Ruixin Liu , Chunmei Cai

The STING-inflammasome axis predominantly functions to transmit signals generated from cGAS-STING-mediated cytosolic DNA recognition, thereby inducing and potentiating inflammasome activation and amplifying immune responses. However, under specific circumstances, the inflammasome can reciprocally modulate STING activity. This dynamic relationship comprises a canonical upstream-downstream activation cascade complemented by bidirectional interactions and feedback loops within the intricate immune regulatory network. Accumulating evidence underscores the pivotal involvement of the STING-inflammasome axis in diverse host defense mechanisms and inflammatory disorders, including autoimmune diseases, sterile inflammatory conditions, carcinogenesis, and neurodegenerative diseases. In this comprehensive review, we systematically summarize the current understanding of the contributions and underlying mechanisms of the STING-inflammasome axis in physiological and pathological processes. Additionally, we conduct an in-depth exploration of the translational potential of targeting this axis for preventive and therapeutic interventions, offering novel insights into future research directions and clinical applications.

sting -炎性小体轴的主要功能是传递由cgas - sting介导的胞质DNA识别产生的信号，从而诱导和增强炎性小体的激活，放大免疫反应。然而，在特定情况下，炎性体可以相互调节STING活性。这种动态关系包括一个典型的上游-下游激活级联，在复杂的免疫调节网络中辅以双向相互作用和反馈回路。越来越多的证据强调sting -炎性小体轴在多种宿主防御机制和炎症性疾病中的关键作用，包括自身免疫性疾病、无菌炎症条件、癌变和神经退行性疾病。在这篇全面的综述中，我们系统地总结了目前对sting -炎性体轴在生理和病理过程中的作用和潜在机制的理解。此外，我们还深入探索了针对该轴进行预防和治疗干预的转化潜力，为未来的研究方向和临床应用提供了新的见解。

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引用次数: 0

Cognitive impairment in systemic autoimmune and inflammatory diseases: A narrative review focused on ANCA-associated vasculitis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and Behçet's disease 系统性自身免疫性和炎症性疾病中的认知障碍：一项关于anca相关血管炎、结节病、Sjögren综合征、系统性硬化症和behaperet病的叙述性综述。

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-05 DOI: 10.1016/j.autrev.2025.103899

Marion Camard , Fanny Urbain , Nicolas Noel

Cognitive impairment is an increasingly recognized feature of systemic autoimmune and inflammatory diseases, yet remains underdiagnosed and insufficiently studied beyond systemic lupus erythematosus. In this narrative review, we explore the prevalence, clinical profiles, and pathophysiological mechanisms of cognitive dysfunction in five systemic diseases: ANCA-associated vasculitis (AAV), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), sarcoidosis, and Behçet's disease (BD). We conducted a structured literature search in PubMed and Embase to identify relevant studies published between 1954 and 2024. Reported prevalence varies widely: ∼30 % in AAV, 0–35 % in sarcoidosis, 10–80 % in pSS, 8–65 % in SSc, and 30–100 % in BD. Executive dysfunction and attention deficits predominate. In some cases—particularly in AAV and BD—cognitive decline may reflect direct central nervous system involvement, but many patients report cognitive complaints without overt neurological manifestations or imaging abnormalities. Proposed mechanisms include blood-brain barrier disruption, cytokine-driven neuroinflammation (notably IL-6, TNF-α, IFN-γ, BAFF), autoantibody-mediated synaptic toxicity, and cerebral hypoperfusion linked to small-vessel vasculopathy. Glial activation and neuroimmune dysregulation are recurring findings in animal models and functional imaging studies. White matter lesions and abnormal brain perfusion on MRI or SPECT are frequently observed in asymptomatic patients. Comorbid symptoms such as depression, fatigue, pain, and small fiber neuropathy may exacerbate or mimic cognitive dysfunction. Despite its prevalence and impact on quality of life, cognitive dysfunction is rarely screened, partly due to a lack of standardized tools. Harmonized neurocognitive assessment protocols and longitudinal studies are urgently needed to improve understanding, detection, and management of cognitive impairment, and support its integration into routine care.

认知障碍是系统性自身免疫性疾病和炎症性疾病的一个日益被认识的特征，但除了系统性红斑狼疮之外，认知障碍仍未得到充分的诊断和研究。在这篇叙述性综述中，我们探讨了五种全身性疾病中认知功能障碍的患病率、临床概况和病理生理机制：anca相关性血管炎（AAV）、原发性Sjögren综合征（pSS）、系统性硬化症（SSc）、结节病和behet病（BD）。我们在PubMed和Embase中进行了结构化的文献检索，以确定1954年至2024年间发表的相关研究。报告的患病率差异很大：AAV为~30 %，结节病为0-35 %，pSS为10-80 %，SSc为8-65 %，BD为30-100 %。以执行功能障碍和注意缺陷为主。在一些病例中，尤其是AAV和bd患者，认知能力下降可能直接反映中枢神经系统受累，但许多患者报告的认知能力主诉没有明显的神经系统表现或影像学异常。提出的机制包括血脑屏障破坏、细胞因子驱动的神经炎症（特别是IL-6、TNF-α、IFN-γ、BAFF）、自身抗体介导的突触毒性以及与小血管病变相关的脑灌注不足。神经胶质活化和神经免疫失调是动物模型和功能成像研究中反复出现的发现。在无症状的患者中，MRI或SPECT经常观察到白质病变和脑灌注异常。合并症如抑郁、疲劳、疼痛和小纤维神经病变可加重或模仿认知功能障碍。尽管认知功能障碍很普遍，对生活质量也有影响，但很少对其进行筛查，部分原因是缺乏标准化的工具。迫切需要统一的神经认知评估方案和纵向研究，以提高对认知障碍的理解、检测和管理，并支持将其纳入常规护理。

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引用次数: 0

Systemic auto-inflammatory diseases, auto-immune diseases and immune deficiencies: From independent to overlapped diseases approach 全身性自身炎性疾病、自身免疫性疾病和免疫缺陷：从独立疾病到重叠疾病的途径。

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews

Pub Date : 2025-08-05 DOI: 10.1016/j.autrev.2025.103901

Anne-Sophie Parentelli , Anne-Aurélie Lopes , Frédéric Rieux-Laucat , Olivier Hermine

Systemic AutoInflammatory Diseases (SAIDs), AutoImmune Diseases (AIDs), and Primary Immune Deficiencies (PIDs) were formely considered independent, even opposing, conditions. SAIDs were associated with the innate immune system, involving dysregulation of inflammation and recurrent episodes of systemic inflammation without an infectious process. Their original definition did not involve autoreactive cells or autoantibodies. In contrast, PIDs were characterised by defects in the adaptive or innate immune system, leading to recurrent infections and immune dysfunction. AIDs were inflammatory diseases also characterised by dysregulation of the immune system attacking its own tissues through autoreactive cells or autoantibodies. Nevertheless, advancements in genetics and a deeper understanding of T-cell development and signalling, immune tolerance, the complement pathway and inflammation have revealed that these conditions are overlapping diseases with shared immune system dysfunctions. These diseases now represent a continuum within a broader spectrum of disorders known as “Inborn Errors of Immunity”. However, this term is not suitable as it does not fully encompass cases arising from somatic mutations and can be stigmatising for patients. Therefore, we propose the terms “Primary Immune Deficiencies and Dysregulations” (PIDDs) or simply “Primary Immune Disorders” (PIDs) as more appropriate alternatives.

Thus, this article aims to describe known diseases where autoimmunity, autoinflammation and primary immunodeficiencies overlap, along with some mechanisms that may explain these interconnections. To our knowledge, no comprehensive reviews on this topic currently exist, despite its significance in modifying our understanding of these diseases, their treatment, and associated research.

系统性自身炎症性疾病（said）、自身免疫性疾病（AIDs）和原发性免疫缺陷（pid）以前被认为是独立的，甚至是对立的。甾体抗炎药与先天免疫系统有关，包括炎症失调和无感染过程的全身炎症反复发作。他们最初的定义不包括自身反应性细胞或自身抗体。相比之下，pid的特征是适应性或先天免疫系统的缺陷，导致复发性感染和免疫功能障碍。艾滋病是炎症性疾病，其特征是免疫系统失调，通过自身反应性细胞或自身抗体攻击自身组织。然而，遗传学的进步和对t细胞发育和信号传导、免疫耐受、补体途径和炎症的更深入理解表明，这些疾病是具有共同免疫系统功能障碍的重叠疾病。这些疾病现在代表了被称为“先天性免疫错误”的更广泛的疾病范围内的一个连续体。然而，这个术语并不合适，因为它不完全包括由体细胞突变引起的病例，并且可能给患者带来耻辱。因此，我们建议“原发性免疫缺陷和失调”（PIDDs）或简单地“原发性免疫疾病”（pid）作为更合适的替代术语。因此，本文旨在描述自身免疫、自身炎症和原发性免疫缺陷重叠的已知疾病，以及可能解释这些相互联系的一些机制。据我们所知，目前还没有关于这一主题的全面综述，尽管它在改变我们对这些疾病、其治疗和相关研究的理解方面具有重要意义。

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引用次数: 0