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Anti-Synthetase Syndrome—Advancing Disease Phenotyping, Classification and Treatment 抗合成酶综合征进展性疾病的分型、分型及治疗。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2026-01-03 DOI: 10.1111/1756-185x.70538
Iris Yan Ki Tang, Lijun Liu
<p>Anti-synthetase syndrome (ASyS) is characterized by the presence of antibodies against aminoacyl transfer RNA (tRNA) synthetase and distinct clinical constellations including interstitial lung disease (ILD), myositis, arthritis, mechanic's hands, fever and raynaud's phenomenon (RP). Since the discovery of anti-histidyl-tRNA synthetase (Anti-Jo1) antibody four decades ago, tremendous progress was made in discovering additional anti-synthetase antibodies [<span>1</span>]. There are 20 different aminoacyl-tRNA synthetase enzymes, and 10 distinct anti-synthetase antibodies (ASA) have been identified so far (Table 1). These antibodies are central to disease classification and may influence clinical phenotypes. There are evolving insights into pathophysiology, clinical heterogeneity, and treatment approaches in ASyS. This article aims to review and discuss the recent research advancements in disease sub-phenotyping, classification and therapeutics in ASyS.</p><p>ASyS exhibits significant clinical heterogeneity with varying disease courses and clinical manifestations among patients. Patients with non-Jo1 ASA were previously reported to have a worse survival than Jo1 patients (10-year cumulative survival of 47% vs. 70%, <i>p</i> < 0.005) by Aggarwal et al. [<span>2</span>], probably related to a delay in diagnosis by 8 months in the non-Jo1 positive patients. However, data from a multicenter registry in Hong Kong did not identify a similar survival difference between Jo1 and non-Jo1 positive patients [<span>3</span>]. Clinical phenotypes might exert a greater impact on survival than the presence of specific ASA. Wu et al. performed cluster analysis on more than 700 ASyS patients from China and identified three unique clinical phenotypes independent of ASA specificity: rapidly-progressive ILD (RP-ILD) cluster (23.7% of patients), dermatomyositis (DM)-like cluster (14.5%) and arthritis cluster (61.8%) [<span>4</span>]. The worst prognosis was observed in the RP-ILD cluster with a 10-year survival rate of 37.0%, compared to 69.5% in the DM-like cluster and 87.4% in the arthritis cluster, but the survival rates were comparable among different ASA. Transcriptomic analysis also revealed distinct gene signatures and biological processes in each cluster. Gene signatures implicated in coagulation and platelet activation were enhanced in the RP-ILD cluster, pathways related to viral infection and interferon-mediated signaling were enriched in the DM-like cluster, and lastly, B cell receptor signaling pathways were upregulated in the arthritis cluster. Whether or not the distinct biological pathways can predict treatment responses to targeted therapy, such as janus kinase inhibitors (JAKi) in the DM-like cluster or anti-CD20 in the arthritis cluster will require further research.</p><p>Apart from predicting prognosis, clinical manifestations are crucial in disease classification though there are controversies on universally accepted classification criteria of
抗合成酶综合征（ASyS）的特点是存在针对氨基酰基转移RNA （tRNA）合成酶的抗体，并有明显的临床症状，包括间质性肺病（ILD）、肌炎、关节炎、机械性手、发烧和雷诺现象（RP）。自从四十年前发现抗组氨酸- trna合成酶（Anti-Jo1）抗体以来，在发现其他抗合成酶抗体[1]方面取得了巨大进展。目前已经鉴定出20种不同的氨基酰基- trna合成酶，10种不同的抗合成酶抗体（ASA）（表1）。这些抗体是疾病分类的核心，并可能影响临床表型。对ASyS的病理生理学、临床异质性和治疗方法有了不断发展的见解。本文旨在综述和讨论近年来在ASyS疾病亚表型、分类和治疗方面的研究进展。ASyS具有明显的临床异质性，患者的病程和临床表现各不相同。Aggarwal等人曾报道，非Jo1型ASA患者的生存率低于Jo1型患者（10年累积生存率为47%对70%，p &lt; 0.005），这可能与非Jo1阳性患者的诊断延迟8个月有关。然而，来自香港多中心注册中心的数据未发现Jo1和非Jo1阳性患者之间存在类似的生存差异[3]。临床表型可能比特异性ASA的存在对生存产生更大的影响。Wu等人对来自中国的700多名ASyS患者进行了聚类分析，确定了三种独立于ASA特异性的独特临床表型：快速进行性ILD （RP-ILD）集群（23.7%的患者）、皮肌炎（DM）样集群（14.5%）和关节炎集群（61.8%）[4]。RP-ILD组预后最差，10年生存率为37.0%，dm样组为69.5%，关节炎组为87.4%，但不同ASA组的生存率具有可比性。转录组学分析还揭示了每个簇的不同基因特征和生物学过程。与凝血和血小板激活相关的基因特征在RP-ILD集群中增强，与病毒感染和干扰素介导的信号通路在dm样集群中富集，最后，B细胞受体信号通路在关节炎集群中上调。不同的生物学途径是否可以预测靶向治疗的治疗反应，如dm样簇中的janus激酶抑制剂（JAKi）或关节炎簇中的抗cd20，将需要进一步的研究。除了预测预后外，临床表现对疾病的分类也至关重要，但对ASyS的普遍接受的分类标准存在争议，这给研究和临床试验的入组带来了很大的障碍。多年来发布了多个ASyS分类标准。2010年，Connors等人根据ASA阳性和以下任何一项对ASyS进行分类：根据Bohan和Peter标准的肌炎、ILD的存在、关节炎、不明原因的持续发烧、RP或机械性手bb0。次年，Solomon等人制定了另一套分类标准，将肌炎或ILD定义为主要标准，而将关节炎、RP和机械性手视为次要标准。ASA存在两个主要标准，或一个主要标准加两个次要标准被归类为ASyS[6]。然而，这些标准不是使用数据驱动的方法制定的。美国风湿病学会（ACR）和欧洲风湿病协会联盟（EULAR）于2017年发布了第一个经过验证的特发性炎症性肌病（IIM）分类标准。抗jo1抗体的存在，以及典型的DM皮肤表现、肌肉无力的模式和肌肉酶升高有助于疾病分类。然而，2017年EULAR/ACR标准不包括ILD或非jo1 ASA的存在，也没有将ASyS定义为独特的IIM亚型。最近，一种新的抗合成酶综合征（CLASS）分类标准被提出，以解决目前ASyS分类的空白[8]。一个包含2000多名ASyS患者和对照组的大型国际数据库（其中16.7%为亚洲人）被用来确定定义ASyS的关键临床和血清学变量。采用临床（ILD、肌肉受累、关节受累、梅克氏手、炎症性皮疹、RP、不明原因发热和肺动脉高压）和血清学域（抗jo1和非抗jo1抗体、抗ro52或细胞质型抗核抗体（ANA）的存在）加权评分系统进行疾病分类。 虽然与ASA阳性相比，抗ro52阳性或抗ANA阳性的加权评分较低，但在一些肌炎特异性抗体检测不广泛的APLAR区域，将抗ro52阳性或抗ANA阳性纳入细胞质模式可能有助于ASyS的分类。然而，在新分类标准最终发布后，特别是未包括在CLASS数据库中的人群（如中国人或东南亚人）的外部验证，在广泛应用于研究和临床试验之前是必不可少的。由于缺乏来自随机对照试验的证据来指导ASyS的治疗，疾病表型和分类的进展可能会促进ASyS的治疗发展。主要器官受累的存在，如大约90%的ASyS患者报告的ILD[3,4]，通常决定了治疗的强度。糖皮质激素（GCs）通常被用作初始治疗。常规的免疫抑制剂，例如霉酚酸酯（MMF）或钙调磷酸酶抑制剂（CNI），经常被添加；最近的一项系统综述显示了改善肺功能参数的潜在有效性，但与常规免疫抑制剂[9]的有效性没有决定性差异。环磷酰胺（CYC）通常用于严重的ASyS-ILD，而生物制剂和janus激酶抑制剂（JAKi）的使用正在兴起。CYC和利妥昔单抗对用力肺活量（FVC）和肺弥散量（DLCO）的改善程度相似。另一项回顾性队列研究报道，在抗jo1 + ASyS患者[10]中，抗cd20比传统免疫抑制剂更有效地实现低疾病活动性（LDA）和减少GCs剂量。值得注意的是，本研究建议使用LDA作为主要终点，这一概念在其他风湿病条件下得到了很好的研究。ASyS中LDA的定义和长期效益值得进一步研究。在20例ASyS-ILD患者中，与安慰剂相比，Abatacept在第48周有改善FVC和DLCO的趋势，但在第24周没有。在病例报告bbb中，Tocilizumab显示出对难治性ASyS的关节、肌肉和肺部受累的潜在疗效。据报道，在一项回顾性队列研究中，JAKi改善了20例难治性ASyS患者中14例的皮疹、肌炎和ILD。未来的ASyS研究将验证新的分类标准，并探索基于不同临床表型的靶向治疗方法，这对改善患者预后非常重要。唐燕琪：构思、写作-原稿、写作-审稿、编辑。刘丽君：写作-原稿，写作-审稿，编辑。作者声明无利益冲突。数据共享不适用于本文，因为在当前研究中没有生成或分析数据集。
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引用次数: 0
Abnormal Resting-State Functional Connectivity Between the Dorsal Anterior Cingulate Cortex and the Limbic System Contributes to Pain and Emotion Regulation Impairment in Fibromyalgia Patients 前扣带背侧皮层与边缘系统之间的异常静息状态功能连接与纤维肌痛患者疼痛和情绪调节功能障碍有关。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2026-01-02 DOI: 10.1111/1756-185x.70531
Yu Wang, Yixin Zhou, Aihui Liu, Chengliang Mao, Shinan Li, Shan Huang, Xingyi Zhu, Hongyang Jiang, Zhenhua Ying

Objectives

The subdivisions of the anterior cingulate cortex (ACC) are involved in distinct functions in the processing of chronic pain and regulation of emotions. However, the specific impact of each ACC subdivision on fibromyalgia (FM) remains unclear. This study aimed to systematically investigate the abnormal resting-state functional connectivity (rsFC) patterns between the ACC (and its subregions) and other chronic-pain-related limbic cortices and subcortical nuclei in patients with FM.

Methods

Resting-state functional magnetic resonance imaging (fMRI) was conducted in 31 patients diagnosed with fibromyalgia (FM) and 32 demographically matched healthy controls (HCs). Using subdivisions of the anterior cingulate cortex (ACC) as regions of interest, we employed a seed-based resting-state functional connectivity (rsFC) approach to identify alterations in connectivity between limbic cortex and subcortical nuclei. A two-sample t-test was applied to compare functional connectivity differences between the two groups. Additionally, Pearson correlation analysis was performed to examine the relationships between rsFC alterations and measures of executive function and clinical symptom severity.

Results

Patients with FM demonstrated aberrant rsFC of the dorsal ACC (dACC) with the limbic system, notably the amygdala (t = 2.840, SE = 0.942, p = 0.007), parahippocampal gyrus (t = 2.340, SE = 0.905, p = 0.024), and insula (t = 2.159, SE = 0.835, p = 0.036). Subregion analyses further revealed heightened connectivity of the anterior midcingulate cortex (aMCC) with the parahippocampal gyrus (t = 2.737, SE = 1.064, p = 0.009), and increased connectivity of the superior anterior cingulate cortex (supACC) with the insula (t = 2.596, SE = 0.706, p = 0.013) and amygdala (t = 2.398, SE = 0.812, p = 0.021), which were significantly associated with pain severity and depressive symptoms in FM.

Conclusion

This study revealed specific abnormalities in the rsFC between the dACC and the limbic cortices and subcortical nuclei in FM patients. The heightened connectivity of the aMCC with the parahippocampal gyrus and of the supACC with the insula and amygdala was closely associated with the regulation of emotion and processing of chronic pain.

目的：前扣带皮层（ACC）的分支在慢性疼痛加工和情绪调节中具有不同的功能。然而，每个ACC细分对纤维肌痛（FM）的具体影响尚不清楚。本研究旨在系统探讨FM患者ACC（及其亚区）与其他慢性疼痛相关边缘皮质和皮质下核之间的异常静息状态功能连接（rsFC）模式。方法：对31例诊断为纤维肌痛（FM）的患者和32例人口统计学匹配的健康对照（hc）进行静息状态功能磁共振成像（fMRI）检查。使用前扣带皮层（ACC）的细分作为感兴趣的区域，我们采用基于种子的静息状态功能连接（rsFC）方法来识别边缘皮层和皮层下核之间连接的变化。采用双样本t检验比较两组之间的功能连接差异。此外，进行Pearson相关分析以检验rsFC改变与执行功能测量和临床症状严重程度之间的关系。结果：FM患者的背侧ACC （dACC）与边缘系统的rsFC均出现异常，尤其是杏仁核（t = 2.840, SE = 0.942, p = 0.007）、海马旁回（t = 2.340, SE = 0.905, p = 0.024）和脑岛（t = 2.159, SE = 0.835, p = 0.036）。亚区分析进一步显示，前扣带皮层（aMCC）与海马旁回的连通性增强（t = 2.737, SE = 1.064, p = 0.009），上扣带前皮层（supACC）与脑岛（t = 2.596, SE = 0.706, p = 0.013）和杏仁核（t = 2.398, SE = 0.812, p = 0.021）的连通性增强，这与FM患者的疼痛程度和抑郁症状显著相关。结论：本研究揭示了FM患者dACC与边缘皮层和皮质下核之间的rsFC的特异性异常。aMCC与海马旁回、supACC与脑岛和杏仁核的高度连通性与情绪调节和慢性疼痛处理密切相关。
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引用次数: 0
Supplement: The 27th Asia-Pacific League of Associations for Rheumatology Congress (APLAR) 2025, 3-7 September 2025, Fukuoka, Japan. 第27届亚太风湿病协会联盟大会（APLAR） 2025, 2025年9月3-7日，日本福冈。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2026-01-01 DOI: 10.1111/1756-185x.70440
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引用次数: 0
Beyond the Surface: The Dual Challenge of Dysphagia and Acrokeratosis 表面之外：吞咽困难和角化症的双重挑战。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2026-01-01 DOI: 10.1111/1756-185x.70533
Joban Deol, Deepak Moka, G. S. R. S. N. K. Naidu, Varun Dhir, Shefali Sharma, Aman Sharma, Sanjay Jain
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引用次数: 0
Supplement: The 27th Asia-Pacific League of Associations for Rheumatology Congress (APLAR) 2025, 3-7 September 2025, Fukuoka, Japan. 第27届亚太风湿病协会联盟大会（APLAR） 2025, 2025年9月3-7日，日本福冈。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2026-01-01 DOI: 10.1111/1756-185x.70439
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引用次数: 0
Supplement: The 27th Asia-Pacific League of Associations for Rheumatology Congress (APLAR) 2025, 3-7 September 2025, Fukuoka, Japan. 第27届亚太风湿病协会联盟大会（APLAR） 2025, 2025年9月3-7日，日本福冈。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2026-01-01 DOI: 10.1111/1756-185x.70438
{"title":"Supplement: The 27th Asia-Pacific League of Associations for Rheumatology Congress (APLAR) 2025, 3-7 September 2025, Fukuoka, Japan.","authors":"","doi":"10.1111/1756-185x.70438","DOIUrl":"https://doi.org/10.1111/1756-185x.70438","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 Suppl 1 ","pages":"e70438"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Supplement: The 27th Asia-Pacific League of Associations for Rheumatology Congress (APLAR) 2025, 3-7 September 2025, Fukuoka, Japan. 第27届亚太风湿病协会联盟大会（APLAR） 2025, 2025年9月3-7日，日本福冈。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2026-01-01 DOI: 10.1111/1756-185x.70437
{"title":"Supplement: The 27th Asia-Pacific League of Associations for Rheumatology Congress (APLAR) 2025, 3-7 September 2025, Fukuoka, Japan.","authors":"","doi":"10.1111/1756-185x.70437","DOIUrl":"https://doi.org/10.1111/1756-185x.70437","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 Suppl 1 ","pages":"e70437"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Case Report: Fulminant Lupus Myocarditis With Concomitant Pulmonary Infarction 病例报告：暴发性狼疮性心肌炎伴发肺梗塞。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2026-01-01 DOI: 10.1111/1756-185x.70525
Beyza Parlatır, Adam Türk, Safiye Bakkal, Semih Gülle
{"title":"Case Report: Fulminant Lupus Myocarditis With Concomitant Pulmonary Infarction","authors":"Beyza Parlatır,&nbsp;Adam Türk,&nbsp;Safiye Bakkal,&nbsp;Semih Gülle","doi":"10.1111/1756-185x.70525","DOIUrl":"10.1111/1756-185x.70525","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
SONK-Like Subchondral Osteonecrosis Associated With Immune Checkpoint Inhibition sonk样软骨下骨坏死与免疫检查点抑制相关。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2025-12-31 DOI: 10.1111/1756-185x.70532
Wan-Hao Tsai, Ko-Jen Li
{"title":"SONK-Like Subchondral Osteonecrosis Associated With Immune Checkpoint Inhibition","authors":"Wan-Hao Tsai,&nbsp;Ko-Jen Li","doi":"10.1111/1756-185x.70532","DOIUrl":"10.1111/1756-185x.70532","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Paraneoplastic Amyopathic Dermatomyositis Suspect by Nailfold Capillaroscopy in a Patient With Breast Carcinoma 甲襞毛细血管镜检查怀疑患有乳腺癌的副肿瘤性淀粉性皮肌炎。
IF 2 4区 医学 Q2 RHEUMATOLOGY
International Journal of Rheumatic Diseases
Pub Date : 2025-12-27 DOI: 10.1111/1756-185x.70528
Farzana Shumy, Minhaj Rahim Choudhury, Zahid Amin, Kotaro Matsumoto
{"title":"Paraneoplastic Amyopathic Dermatomyositis Suspect by Nailfold Capillaroscopy in a Patient With Breast Carcinoma","authors":"Farzana Shumy,&nbsp;Minhaj Rahim Choudhury,&nbsp;Zahid Amin,&nbsp;Kotaro Matsumoto","doi":"10.1111/1756-185x.70528","DOIUrl":"10.1111/1756-185x.70528","url":null,"abstract":"","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"29 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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