Journal of autoimmunity最新文献_第8页

Passive maternal immunity in children born to women with systemic autoimmune rheumatic disease – A case-control study 患有系统性自身免疫性风湿病妇女所生儿童的被动母体免疫-一项病例对照研究

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-06-01 Epub Date: 2025-05-22 DOI: 10.1016/j.jaut.2025.103439

Antonia Mazzucato-Puchner , Helene Ramspeck , Valentin Ritschl , Tanja Stamm , Valerie Kuczwara , Alexandra Szlatinay , Peter Mandl , Stephan Blüml , Helmuth Haslacher , Ulrike Baranyi , Veronica Falcone , Daniel Aletaha , Klara Rosta

Introduction

The transplacental transfer of maternal antibodies is essential for neonatal immunity but can be affected by maternal health conditions and pregnancy complications. In women with systemic autoimmune rheumatic diseases (SARD) this transfer may be influenced by the autoimmune condition itself and/or the immunosuppressive therapies administered during pregnancy.

Objective

This study aimed to assess the transplacental transfer and efficacy of vaccine-induced antibodies in pregnant women with SARD compared to healthy controls.

Methods

We enrolled pregnant women with and without SARD pregnancy. Venous blood samples were collected during the third trimester, and umbilical cord blood was obtained postpartum. Antibody titers were assessed using Roche SARS-CoV-2 RBD ECLIA for SARS-CoV-2 and DiaSorin kits for varicella-zoster virus and rubella.

Results

25 pregnant women with SARD and 30 healthy controls were analyzed. Of these, 25 women were vaccinated against SARS- CoV-2 during pregnancy. Transplacental antibody transfer was effective in the SARD and in the control groups. Rubella and SARS-CoV-2 antibody levels showed no significant differences in either maternal or cord blood samples. Varicella-zoster virus antibody levels were higher in SARD maternal and cord sera than in controls. In all cases maternal and neonatal antibody titers were highly correlated (p < 0.001).

Conclusions

Our findings suggest effective maternal-to-fetal antibody transfer in women with SARD both for existing antibodies (varicella-zoster virus, rubella) as well as newly generated ones (anti-Covid Igs generated after vaccination during pregnancy), indicating robust passive immunity in their newborns.

母体抗体经胎盘移植对新生儿免疫至关重要，但可能受到母体健康状况和妊娠并发症的影响。在患有系统性自身免疫性风湿病（SARD）的妇女中，这种转移可能受到自身免疫性疾病本身和/或妊娠期间给予的免疫抑制治疗的影响。目的比较SARD孕妇与健康对照者的胎盘移植及疫苗诱导抗体的效果。方法纳入有和无SARD妊娠的孕妇。在妊娠晚期采集静脉血，产后采集脐带血。采用罗氏SARS-CoV-2 RBD ECLIA试剂盒检测SARS-CoV-2抗体滴度，采用水痘-带状疱疹病毒和风疹的DiaSorin试剂盒检测水痘-带状疱疹病毒和风疹。结果对25例SARD孕妇和30例健康对照进行了分析。其中，25名妇女在怀孕期间接种了SARS- CoV-2疫苗。经胎盘抗体转移在SARD组和对照组均有效。在母体和脐带血样本中，风疹和SARS-CoV-2抗体水平均无显著差异。SARD产妇和脐带血清中水痘带状疱疹病毒抗体水平高于对照组。在所有病例中，母亲和新生儿抗体滴度高度相关(p <；0.001)。结论SARD患者既有抗体（水痘-带状疱疹病毒、风疹），也有新生抗体（妊娠期接种疫苗后产生的抗covid - Igs），母体-胎儿抗体转移有效，新生儿具有较强的被动免疫能力。

{"title":"Passive maternal immunity in children born to women with systemic autoimmune rheumatic disease – A case-control study","authors":"Antonia Mazzucato-Puchner , Helene Ramspeck , Valentin Ritschl , Tanja Stamm , Valerie Kuczwara , Alexandra Szlatinay , Peter Mandl , Stephan Blüml , Helmuth Haslacher , Ulrike Baranyi , Veronica Falcone , Daniel Aletaha , Klara Rosta","doi":"10.1016/j.jaut.2025.103439","DOIUrl":"10.1016/j.jaut.2025.103439","url":null,"abstract":"<div><h3>Introduction</h3><div>The transplacental transfer of maternal antibodies is essential for neonatal immunity but can be affected by maternal health conditions and pregnancy complications. In women with systemic autoimmune rheumatic diseases (SARD) this transfer may be influenced by the autoimmune condition itself and/or the immunosuppressive therapies administered during pregnancy.</div></div><div><h3>Objective</h3><div>This study aimed to assess the transplacental transfer and efficacy of vaccine-induced antibodies in pregnant women with SARD compared to healthy controls.</div></div><div><h3>Methods</h3><div>We enrolled pregnant women with and without SARD pregnancy. Venous blood samples were collected during the third trimester, and umbilical cord blood was obtained postpartum. Antibody titers were assessed using Roche SARS-CoV-2 RBD ECLIA for SARS-CoV-2 and DiaSorin kits for varicella-zoster virus and rubella.</div></div><div><h3>Results</h3><div>25 pregnant women with SARD and 30 healthy controls were analyzed. Of these, 25 women were vaccinated against SARS- CoV-2 during pregnancy. Transplacental antibody transfer was effective in the SARD and in the control groups. Rubella and SARS-CoV-2 antibody levels showed no significant differences in either maternal or cord blood samples. Varicella-zoster virus antibody levels were higher in SARD maternal and cord sera than in controls. In all cases maternal and neonatal antibody titers were highly correlated (p < 0.001).</div></div><div><h3>Conclusions</h3><div>Our findings suggest effective maternal-to-fetal antibody transfer in women with SARD both for existing antibodies (varicella-zoster virus, rubella) as well as newly generated ones (anti-Covid Igs generated after vaccination during pregnancy), indicating robust passive immunity in their newborns.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103439"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Machine learning approach to single cell transcriptomic analysis of Sjogren's disease reveals altered activation states of B and T lymphocytes 机器学习方法对干燥病的单细胞转录组学分析揭示了B和T淋巴细胞激活状态的改变

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-06-01 Epub Date: 2025-05-02 DOI: 10.1016/j.jaut.2025.103419

Maxwell McDermott , Wenyi Li , Yin-Hu Wang , Allen Y. Chen , Rodrigo Lacruz , Bettina Nadorp , Stefan Feske

Sjogren's Disease (SjD) is an autoimmune disorder characterized by salivary and lacrimal gland dysfunction and immune cell infiltration leading to gland inflammation and destruction. Although SjD is a common disease, its pathogenesis is not fully understood. In this study, we conducted a single-cell transcriptome analysis of peripheral blood mononuclear cells (PBMC) from patients with SjD and symptomatic non-SjD controls to identify cell types and functional changes involved in SjD pathogenesis. All PBMCs populations showed marked differences in gene expression between SjD patients and controls, particularly an increase in interferon (IFN) signaling gene signatures. T and B cells of SjD patients displayed a depletion of ribosomal gene expression and pathways linked to protein translation. SjD patients had increased frequencies of naive B cells, which featured a unique gene expression profile (GEP) distinct from controls and had hallmarks of B cell hyperactivation. Non-negative matrix factorization (NMF) also identified several non-overlapping GEPs in CD4⁺ and CD8⁺ T cells with differential usage in SjD patients and controls. Of these, only the Th1 activation GEP was enriched in T cells of SjD patients whereas the other two GEPs were depleted in T cells, emphasizing the important role of Th1 cells in SjD. Our study provides evidence for aberrant and unique gene expression patterns in both B and T lymphocytes of SjD patients that point to their altered activation states and may provide new insights into the pathogenesis of SjD.

干燥病（SjD）是一种自身免疫性疾病，以唾液腺和泪腺功能障碍和免疫细胞浸润导致腺体炎症和破坏为特征。虽然SjD是一种常见病，但其发病机制尚不完全清楚。在这项研究中，我们对SjD患者和症状性非SjD对照组的外周血单核细胞（PBMC）进行了单细胞转录组分析，以确定SjD发病过程中涉及的细胞类型和功能变化。所有PBMCs群体在SjD患者和对照组之间的基因表达都有显著差异，特别是干扰素（IFN）信号基因特征的增加。SjD患者的T和B细胞表现出核糖体基因表达和与蛋白质翻译相关的途径的缺失。SjD患者初始B细胞的频率增加，其特征是独特的基因表达谱（GEP）不同于对照组，具有B细胞过度活化的特征。非阴性基质因子分解（NMF）也在SjD患者和对照组的CD4+和CD8+ T细胞中发现了几种非重叠的GEPs。其中，只有Th1激活GEP在SjD患者的T细胞中富集，而其他两种GEP在T细胞中缺失，强调了Th1细胞在SjD中的重要作用。我们的研究为SjD患者B淋巴细胞和T淋巴细胞异常和独特的基因表达模式提供了证据，这些基因表达模式指向了它们激活状态的改变，并可能为SjD的发病机制提供新的见解。

{"title":"Machine learning approach to single cell transcriptomic analysis of Sjogren's disease reveals altered activation states of B and T lymphocytes","authors":"Maxwell McDermott , Wenyi Li , Yin-Hu Wang , Allen Y. Chen , Rodrigo Lacruz , Bettina Nadorp , Stefan Feske","doi":"10.1016/j.jaut.2025.103419","DOIUrl":"10.1016/j.jaut.2025.103419","url":null,"abstract":"<div><div>Sjogren's Disease (SjD) is an autoimmune disorder characterized by salivary and lacrimal gland dysfunction and immune cell infiltration leading to gland inflammation and destruction. Although SjD is a common disease, its pathogenesis is not fully understood. In this study, we conducted a single-cell transcriptome analysis of peripheral blood mononuclear cells (PBMC) from patients with SjD and symptomatic non-SjD controls to identify cell types and functional changes involved in SjD pathogenesis. All PBMCs populations showed marked differences in gene expression between SjD patients and controls, particularly an increase in interferon (IFN) signaling gene signatures. T and B cells of SjD patients displayed a depletion of ribosomal gene expression and pathways linked to protein translation. SjD patients had increased frequencies of naive B cells, which featured a unique gene expression profile (GEP) distinct from controls and had hallmarks of B cell hyperactivation. Non-negative matrix factorization (NMF) also identified several non-overlapping GEPs in CD4<sup>+</sup> and CD8<sup>+</sup> T cells with differential usage in SjD patients and controls. Of these, only the Th1 activation GEP was enriched in T cells of SjD patients whereas the other two GEPs were depleted in T cells, emphasizing the important role of Th1 cells in SjD. Our study provides evidence for aberrant and unique gene expression patterns in both B and T lymphocytes of SjD patients that point to their altered activation states and may provide new insights into the pathogenesis of SjD.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103419"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The role of gut flora-driven Th cell responses in preclinical rheumatoid arthritis 肠道菌群驱动的细胞反应在临床前类风湿关节炎中的作用

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-06-01 Epub Date: 2025-04-28 DOI: 10.1016/j.jaut.2025.103426

Shuanglan Chen , Lijuan Dan , Li Xiang , Qingman He , Dongsen Hu , Yongxiang Gao

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with an immune pathogenesis that evolves over decades. Preclinical RA (PreRA) represents a dynamic immune phase preceding clinical RA, marked by the loss of autoimmune tolerance, the appearance of tissue-invasive effector T cells, and the production of autoantibodies (such as antibodies against citrullinated proteins and rheumatoid factors). Extensive research has demonstrated that gut microbiota influence mucosal T-cell responses, driving the progression of PreRA through multiple mechanisms, including altered intestinal permeability, gene-environment interactions, bacterial antigenic specificity, molecular mimicry, and metabolite production. Environmental risk factors such as smoking, hormonal changes, and high-sodium (Na) diets, may contribute to RA pathogenesis via the gut microbiome. The next challenge in RA research lies in developing therapeutic strategies to intervene during the asymptomatic autoimmune phase, where dietary adjustments, natural compounds, probiotics, and other approaches could effectively modulate gut flora to prevent or delay RA onset.

类风湿性关节炎（RA）是一种慢性自身免疫性炎症性疾病，其免疫发病机制已经发展了几十年。临床前RA （preera）代表临床RA之前的一个动态免疫阶段，其标志是自身免疫耐受性的丧失，组织侵入效应T细胞的出现，以及自身抗体的产生（如针对瓜氨酸蛋白和类风湿因子的抗体）。大量研究表明，肠道微生物群影响粘膜t细胞反应，通过多种机制推动prea的进展，包括肠道通透性改变、基因-环境相互作用、细菌抗原特异性、分子拟态和代谢物产生。环境风险因素，如吸烟、激素变化和高钠饮食，可能通过肠道微生物群促进RA发病。RA研究的下一个挑战在于制定治疗策略，在无症状自身免疫阶段进行干预，其中饮食调整，天然化合物，益生菌和其他方法可以有效调节肠道菌群，以预防或延迟RA发作。

{"title":"The role of gut flora-driven Th cell responses in preclinical rheumatoid arthritis","authors":"Shuanglan Chen , Lijuan Dan , Li Xiang , Qingman He , Dongsen Hu , Yongxiang Gao","doi":"10.1016/j.jaut.2025.103426","DOIUrl":"10.1016/j.jaut.2025.103426","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with an immune pathogenesis that evolves over decades. Preclinical RA (PreRA) represents a dynamic immune phase preceding clinical RA, marked by the loss of autoimmune tolerance, the appearance of tissue-invasive effector T cells, and the production of autoantibodies (such as antibodies against citrullinated proteins and rheumatoid factors). Extensive research has demonstrated that gut microbiota influence mucosal T-cell responses, driving the progression of PreRA through multiple mechanisms, including altered intestinal permeability, gene-environment interactions, bacterial antigenic specificity, molecular mimicry, and metabolite production. Environmental risk factors such as smoking, hormonal changes, and high-sodium (Na) diets, may contribute to RA pathogenesis <em>via</em> the gut microbiome. The next challenge in RA research lies in developing therapeutic strategies to intervene during the asymptomatic autoimmune phase, where dietary adjustments, natural compounds, probiotics, and other approaches could effectively modulate gut flora to prevent or delay RA onset.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103426"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Microbial dysbiosis fuels STING-driven autoinflammation through cyclic dinucleotides 微生物生态失调通过环二核苷酸刺激sting驱动的自身炎症

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-06-01 Epub Date: 2025-05-06 DOI: 10.1016/j.jaut.2025.103434

Takayuki Shibahara , Burcu Temizoz , Shiori Egashira , Koji Hosomi , Jonguk Park , Naz Surucu , Albin Björk , Erdal Sag , Takehiko Doi , Rabia Miray Kisla Ekinci , Sibel Balci , Marjan A. Versnel , Jun Kunisawa , Masahiro Yamamoto , Tomoya Hayashi , Shuichi Ito , Yuji Kamiyama , Kouji Kobiyama , Peter D. Katsikis , Cevayir Coban , Ken J. Ishii

Aberrant activation of the stimulator of interferon genes (STING) pathway is a hallmark of autoinflammatory disorders such as STING-associated vasculopathy with onset in infancy (SAVI), characterized by systemic inflammation affecting blood vessels, skin, and lungs. Despite its clinical significance, the mechanisms linking STING activation to disease pathology remain poorly defined. In this study, we demonstrated that SAVI mice harboring the N153S STING mutation exhibit diverse disease phenotypes, with a subset developing severe colitis and diarrhea alongside exacerbated systemic inflammation. These diarrheal SAVI mice showed pronounced dysbiosis, marked by reduced short-chain fatty acid-producing bacteria and an enrichment of segmented filamentous bacteria. This microbial imbalance was accompanied by elevated levels of both microbial and host-derived cyclic dinucleotides (CDNs), potent activators of the STING pathway. Notably, antibiotic treatment ameliorated inflammation, underscoring the role of dysbiosis in driving STING-mediated autoinflammation. Furthermore, in SAVI patients, elevated systemic microbial and host-derived CDNs were observed. In conditions such as systemic lupus erythematosus (SLE)—a heterogeneous autoimmune disease with potential STING involvement—systemic microbial CDNs were significantly correlated with disease biomarkers, including type I interferon scores and anti-dsDNA antibodies. In contrast, no such correlations were observed in STING-independent conditions like rheumatoid arthritis (RA). Importantly, this study highlights that both microbial and host-derived CDNs are key drivers of STING activation, suggesting that personalized treatment strategies could target cGAS or the microbiome based on a patient's specific CDN profile. These findings position systemic CDNs as valuable biomarkers and therapeutic targets for STING-driven diseases.

干扰素刺激因子（STING）通路的异常激活是自身炎症性疾病的一个标志，如婴儿期发作的STING相关血管病变（SAVI），其特征是影响血管、皮肤和肺部的全身性炎症。尽管具有临床意义，但将STING激活与疾病病理联系起来的机制仍不清楚。在这项研究中，我们证明了携带N153S STING突变的SAVI小鼠表现出多种疾病表型，其中一个亚群发展为严重的结肠炎和腹泻，并伴有加重的全身炎症。这些腹泻的SAVI小鼠表现出明显的生态失调，其特征是短链脂肪酸产生细菌减少，节段丝状细菌丰富。这种微生物失衡伴随着微生物和宿主衍生的环二核苷酸（cdn）水平的升高，cdn是STING途径的有效激活剂。值得注意的是，抗生素治疗改善了炎症，强调了生态失调在驱动sting介导的自身炎症中的作用。此外，在SAVI患者中，观察到系统微生物和宿主来源的cdn升高。在系统性红斑狼疮（SLE）——一种可能涉及STING的异质性自身免疫性疾病——等情况下，系统微生物cdn与疾病生物标志物（包括I型干扰素评分和抗dsdna抗体）显著相关。相比之下，在与sting无关的情况下，如类风湿关节炎（RA），没有观察到这种相关性。重要的是，这项研究强调微生物和宿主来源的CDN都是STING激活的关键驱动因素，这表明个性化治疗策略可以基于患者特定的CDN特征来靶向cGAS或微生物组。这些发现将全身性cdn定位为有价值的生物标志物和sting驱动疾病的治疗靶点。

{"title":"Microbial dysbiosis fuels STING-driven autoinflammation through cyclic dinucleotides","authors":"Takayuki Shibahara , Burcu Temizoz , Shiori Egashira , Koji Hosomi , Jonguk Park , Naz Surucu , Albin Björk , Erdal Sag , Takehiko Doi , Rabia Miray Kisla Ekinci , Sibel Balci , Marjan A. Versnel , Jun Kunisawa , Masahiro Yamamoto , Tomoya Hayashi , Shuichi Ito , Yuji Kamiyama , Kouji Kobiyama , Peter D. Katsikis , Cevayir Coban , Ken J. Ishii","doi":"10.1016/j.jaut.2025.103434","DOIUrl":"10.1016/j.jaut.2025.103434","url":null,"abstract":"<div><div>Aberrant activation of the stimulator of interferon genes (STING) pathway is a hallmark of autoinflammatory disorders such as STING-associated vasculopathy with onset in infancy (SAVI), characterized by systemic inflammation affecting blood vessels, skin, and lungs. Despite its clinical significance, the mechanisms linking STING activation to disease pathology remain poorly defined. In this study, we demonstrated that SAVI mice harboring the N153S STING mutation exhibit diverse disease phenotypes, with a subset developing severe colitis and diarrhea alongside exacerbated systemic inflammation. These diarrheal SAVI mice showed pronounced dysbiosis, marked by reduced short-chain fatty acid-producing bacteria and an enrichment of segmented filamentous bacteria. This microbial imbalance was accompanied by elevated levels of both microbial and host-derived cyclic dinucleotides (CDNs), potent activators of the STING pathway. Notably, antibiotic treatment ameliorated inflammation, underscoring the role of dysbiosis in driving STING-mediated autoinflammation. Furthermore, in SAVI patients, elevated systemic microbial and host-derived CDNs were observed. In conditions such as systemic lupus erythematosus (SLE)—a heterogeneous autoimmune disease with potential STING involvement—systemic microbial CDNs were significantly correlated with disease biomarkers, including type I interferon scores and anti-dsDNA antibodies. In contrast, no such correlations were observed in STING-independent conditions like rheumatoid arthritis (RA). Importantly, this study highlights that both microbial and host-derived CDNs are key drivers of STING activation, suggesting that personalized treatment strategies could target cGAS or the microbiome based on a patient's specific CDN profile. These findings position systemic CDNs as valuable biomarkers and therapeutic targets for STING-driven diseases.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"154 ","pages":"Article 103434"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Mepolizumab versus benralizumab for eosinophilic granulomatosis with polyangiitis (EGPA): A European real-life retrospective comparative study Mepolizumab与benralizumab治疗嗜酸性肉芽肿病合并多血管炎（EGPA）：一项欧洲现实回顾性比较研究

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1016/j.jaut.2025.103398

Irene Mattioli , Maria Letizia Urban , Roberto Padoan , Aladdin J. Mohammad , Carlo Salvarani , Chiara Baldini , Alvise Berti , Paolo Cameli , Marco Caminati , Pascal Cathébras , Fulvia Chieco Bianchi , Francesco Cinetto , Jan Willem Cohen Tervaert , Angelo Coppola , Giulia Costanzo , Vincent Cottin , Claudia Crimi , Stefano Del Giacco , Charlene Desaintjean , Allyson Egan , Barbara Trezzi

Background

Following the results of the MANDARA trial, this real-life study aimed at comparing the effectiveness and safety profile of mepolizumab versus benralizumab in a European EGPA cohort.

Methods

We conducted a retrospective observational comparative study including EGPA patients, who received mepolizumab or benralizumab at the asthma dose. Patients were matched 1:1 by sex, age, BVAS and oral corticosteroid (OCS) dosage at the treatment initiation (T0). Complete response (CR) and partial response (PR), disease activity, OCS, pulmonary parameters, eosinophil count, relapses, and safety outcomes were also compared at 3, 6 and 12 months.

Results

Patients treated with mepolizumab or benralizumab (n = 88 each) were matched: 57 % were females, median age was 54 years (IQR 45–60), median OCS dose 10 (7.5–12.5) and 10 (7–13) mg/day, median BVAS 4 (2–7) and 3 (2–8), respectively. 45.4 % of patients in the mepolizumab group and 51.1 % in the benralizumab group achieved CR or PR at T3, with CR steadily increasing during follow-up for both treatments. At T12, a higher CR rate was found in the benralizumab group (48.1 % vs 32.4 %, p = 0.005). No differences in BVAS, OCS, and respiratory parameters were observed between groups at the different timepoints. Throughout the follow-up, both treatments reduced eosinophil count, although a deeper reduction was found in the benralizumab group at all timepoints (p < 0.0001). Safety profile was comparable between patient groups.

Conclusion

Mepolizumab and benralizumab showed comparable overall effectiveness and safety in EGPA. However, benralizumab achieved a higher CR rate at T12, and a deeper peripheral eosinophil reduction.

在MANDARA试验结果之后，这项现实生活中的研究旨在比较mepolizumab与benralizumab在欧洲EGPA队列中的有效性和安全性。方法我们进行了一项回顾性观察性比较研究，纳入EGPA患者，接受mepolizumab或benralizumab的哮喘剂量。患者按性别、年龄、BVAS和治疗开始时口服皮质类固醇（OCS）剂量（T0）进行1:1匹配。完全缓解（CR）和部分缓解（PR）、疾病活动性、OCS、肺参数、嗜酸性粒细胞计数、复发和安全性结果也在3、6和12个月时进行了比较。结果mepolizumab或benralizumab治疗的患者（各88例）匹配：57%为女性，中位年龄为54岁（IQR 45-60），中位OCS剂量为10（7.5-12.5）和10 (7-13)mg/天，中位BVAS分别为4（2-7）和3（2-8）。45.4%的mepolizumab组患者和51.1%的benralizumab组患者在T3达到CR或PR，在两种治疗的随访期间CR稳步增加。在T12时，benralizumab组的CR率更高（48.1% vs 32.4%, p = 0.005）。各组在不同时间点的BVAS、OCS和呼吸参数均无差异。在整个随访过程中，两种治疗均降低了嗜酸性粒细胞计数，尽管贝纳利珠单抗组在所有时间点均有更深程度的降低(p <；0.0001)。患者组间的安全性具有可比性。结论mepolizumab和benralizumab在EGPA治疗中具有相当的总体有效性和安全性。然而，贝纳利珠单抗在T12时实现了更高的CR率，以及更深的外周嗜酸性粒细胞减少。

{"title":"Mepolizumab versus benralizumab for eosinophilic granulomatosis with polyangiitis (EGPA): A European real-life retrospective comparative study","authors":"Irene Mattioli , Maria Letizia Urban , Roberto Padoan , Aladdin J. Mohammad , Carlo Salvarani , Chiara Baldini , Alvise Berti , Paolo Cameli , Marco Caminati , Pascal Cathébras , Fulvia Chieco Bianchi , Francesco Cinetto , Jan Willem Cohen Tervaert , Angelo Coppola , Giulia Costanzo , Vincent Cottin , Claudia Crimi , Stefano Del Giacco , Charlene Desaintjean , Allyson Egan , Barbara Trezzi","doi":"10.1016/j.jaut.2025.103398","DOIUrl":"10.1016/j.jaut.2025.103398","url":null,"abstract":"<div><h3>Background</h3><div>Following the results of the MANDARA trial, this real-life study aimed at comparing the effectiveness and safety profile of mepolizumab <em>versus</em> benralizumab in a European EGPA cohort.</div></div><div><h3>Methods</h3><div>We conducted a retrospective observational comparative study including EGPA patients, who received mepolizumab or benralizumab at the asthma dose. Patients were matched 1:1 by sex, age, BVAS and oral corticosteroid (OCS) dosage at the treatment initiation (T0). Complete response (CR) and partial response (PR), disease activity, OCS, pulmonary parameters, eosinophil count, relapses, and safety outcomes were also compared at 3, 6 and 12 months.</div></div><div><h3>Results</h3><div>Patients treated with mepolizumab or benralizumab (n = 88 each) were matched: 57 % were females, median age was 54 years (IQR 45–60), median OCS dose 10 (7.5–12.5) and 10 (7–13) mg/day, median BVAS 4 (2–7) and 3 (2–8), respectively. 45.4 % of patients in the mepolizumab group and 51.1 % in the benralizumab group achieved CR or PR at T3, with CR steadily increasing during follow-up for both treatments. At T12, a higher CR rate was found in the benralizumab group (48.1 % vs 32.4 %, p = 0.005). No differences in BVAS, OCS, and respiratory parameters were observed between groups at the different timepoints. Throughout the follow-up, both treatments reduced eosinophil count, although a deeper reduction was found in the benralizumab group at all timepoints (p < 0.0001). Safety profile was comparable between patient groups.</div></div><div><h3>Conclusion</h3><div>Mepolizumab and benralizumab showed comparable overall effectiveness and safety in EGPA. However, benralizumab achieved a higher CR rate at T12, and a deeper peripheral eosinophil reduction.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103398"},"PeriodicalIF":7.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miR-143-3p boosts extracellular vesicles to improve the dermal fibrosis of localized scleroderma miR-143-3p促进细胞外囊泡，改善局限性硬皮病真皮纤维化

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-05-01 Epub Date: 2025-04-23 DOI: 10.1016/j.jaut.2025.103422

Jiahui Jin , Zhe Wang , Yifan Liu , Jie Chen , Miao Jiang , Lixia Lu , Jingying Xu , Furong Gao , Juan Wang , Jieping Zhang , Guo-Tong Xu , Caixia Jin , Haibin Tian , Jingjun Zhao , Qingjian Ou

Localized scleroderma (LoSc) is an autoimmune disease that features extensive fibrosis of the skin. Due to its severity and limited understanding, no effective treatments have been developed to date. Bone marrow mesenchymal stem cells (BMSCs) derived extracellular vesicles (EVs) have been demonstrated promising therapeutic effects on the LoSc mouse model in our previous study. However, identifying the targets and underlying mechanisms of EVs remains a significant challenge for therapeutic applications. miR-143-3p, a critical and abundant factor in BMSC-EVs identified through miRNA sequencing, mediates antifibrotic effects in a LoSc mouse model and is significantly lacking in the dermis of LoSc patients. This microRNA inhibits myofibroblast formation and collagen synthesis, contributing to the therapeutic effects of BMSC-EVs in the LoSc mouse model. Moreover, miR-143-3p-reinforced BMSC-EVs demonstrated enhanced therapeutic efficacy compared to normal BMSC-EVs, reducing dermal thickening, collagen deposition, fibroblast differentiation into myofibroblasts, and promoting skin tissue remodeling. IGF1R, highly expressed in the skin of LoSc, was identified as a potential target of miR-143-3p and was inhibited by miR-143-3p-reinforced EVs, thereby modulating the IGF1/IGF1R-AKT/MAPK pathway. In conclusion, miR-143-3p-enriched EVs could be a more efficient candidate for treating dermal fibrosis in LoSc.

局限性硬皮病（LoSc）是一种以皮肤广泛纤维化为特征的自身免疫性疾病。由于其严重程度和认识有限，迄今为止尚未开发出有效的治疗方法。在我们之前的研究中，骨髓间充质干细胞（BMSCs）衍生的细胞外囊泡（EVs）已被证明对LoSc小鼠模型有良好的治疗作用。然而，确定ev的靶点和潜在机制仍然是治疗应用的重大挑战。miR-143-3p是通过miRNA测序发现的bmsc - ev中一个关键且丰富的因子，在LoSc小鼠模型中介导抗纤维化作用，在LoSc患者真皮中明显缺乏。该microRNA抑制肌成纤维细胞形成和胶原合成，有助于bmsc - ev在LoSc小鼠模型中的治疗作用。此外，与正常bmsc - ev相比，mir -143-3p增强的bmsc - ev表现出更强的治疗效果，减少真皮增厚、胶原沉积、成纤维细胞分化为肌成纤维细胞，促进皮肤组织重塑。IGF1R在LoSc皮肤中高表达，被认为是miR-143-3p的潜在靶标，并被miR-143-3p增强的ev抑制，从而调节IGF1/IGF1R- akt /MAPK通路。总之，mir -143-3p富集的ev可能是治疗LoSc真皮纤维化的更有效的候选者。

{"title":"miR-143-3p boosts extracellular vesicles to improve the dermal fibrosis of localized scleroderma","authors":"Jiahui Jin , Zhe Wang , Yifan Liu , Jie Chen , Miao Jiang , Lixia Lu , Jingying Xu , Furong Gao , Juan Wang , Jieping Zhang , Guo-Tong Xu , Caixia Jin , Haibin Tian , Jingjun Zhao , Qingjian Ou","doi":"10.1016/j.jaut.2025.103422","DOIUrl":"10.1016/j.jaut.2025.103422","url":null,"abstract":"<div><div>Localized scleroderma (LoSc) is an autoimmune disease that features extensive fibrosis of the skin. Due to its severity and limited understanding, no effective treatments have been developed to date. Bone marrow mesenchymal stem cells (BMSCs) derived extracellular vesicles (EVs) have been demonstrated promising therapeutic effects on the LoSc mouse model in our previous study. However, identifying the targets and underlying mechanisms of EVs remains a significant challenge for therapeutic applications. miR-143-3p, a critical and abundant factor in BMSC-EVs identified through miRNA sequencing, mediates antifibrotic effects in a LoSc mouse model and is significantly lacking in the dermis of LoSc patients. This microRNA inhibits myofibroblast formation and collagen synthesis, contributing to the therapeutic effects of BMSC-EVs in the LoSc mouse model. Moreover, miR-143-3p-reinforced BMSC-EVs demonstrated enhanced therapeutic efficacy compared to normal BMSC-EVs, reducing dermal thickening, collagen deposition, fibroblast differentiation into myofibroblasts, and promoting skin tissue remodeling. IGF1R, highly expressed in the skin of LoSc, was identified as a potential target of miR-143-3p and was inhibited by miR-143-3p-reinforced EVs, thereby modulating the IGF1/IGF1R-AKT/MAPK pathway. In conclusion, miR-143-3p-enriched EVs could be a more efficient candidate for treating dermal fibrosis in LoSc.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103422"},"PeriodicalIF":7.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Long-term efficacy and safety of colchicine and anti-IL-1 blockers in FMF: results from the Eurofever multicenter observational study 秋水仙碱和抗il -1阻滞剂治疗FMF的长期疗效和安全性：来自欧洲热多中心观察研究的结果

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-05-01 Epub Date: 2025-04-18 DOI: 10.1016/j.jaut.2025.103421

Marta Bustaffa , Saverio La Bella , Yagmur Bayindir , Gayane Amaryan , Romina Gallizzi , Efimia Papadopoulou-Alataki , Giovanna Fabio , Naiera Assalia , Gil Amarilyo , Sevcan Bakkaloglu , Milos Jesenak , Luciana Breda , Jordi Anton , Elizabeth Legger , Maria Alessio , Gabriele Simonini , Donato Rigante , Laura Obici , Jasmin Kuemmerle-Deschner , Ozgur Kasapcopur , Seza Ozen

Introduction

The majority of currently available data on familial Mediterranean fever (FMF) come from retrospective national or international studies.

Methods

An observational study collected data on the Eurofever international FMF cohort. Patients fulfilling genetic and clinical Eurofever criteria were considered as FMF+. Patients not fulfilling clinical and/or genetic (one VUS or benign variants or negative for MEFV variants) criteria were considered as FMF-. Data on compliance to treatment and quality of life were also recorded.

Results

Since November 2024, 876 FMF patients (466 M, 410 F) were enrolled, with a mean follow-up of 2.9 ± 3.1 years. 730 (84 %) patients were classified as FMF+, 146 (16 %) as FMF-, with significant differences in the prevalence of clinical manifestations and treatment response between the two groups. At the last follow-up, 433 patients (50.6 %) still had some disease activity. At the last follow-up 749 (85.5 %) patients received colchicine with a relative under dosage of the drug. Anti-IL-1 treatment was reported in 133 patients (15.2 %), mostly canakinumab (117, 13.4 %). Treatment compliance was generally satisfactory, and adverse events were generally mild.

Conclusions

Patients with an FMF-like phenotype who lack genetic confirmation display significant differences in clinical features and duration of attacks and show a less response to treatment during their disease course in respect, and thus, should be considered as FMF-mimics and investigated for other causes. Longitudinal data provides a more detailed comprehension of the long-term burden of FMF and the impact of treatment on disease activity and patients' quality of life.

目前可获得的关于家族性地中海热（FMF）的大部分数据来自回顾性的国家或国际研究。方法一项观察性研究收集了欧洲热国际FMF队列的数据。满足遗传和临床欧洲热标准的患者被认为是FMF+。不符合临床和/或遗传（一个VUS或良性变异或MEFV变异阴性）标准的患者被认为是FMF-。对治疗依从性和生活质量的数据也进行了记录。结果自2024年11月至今，共纳入FMF患者876例（466例M， 410例F），平均随访2.9±3.1年。FMF+组730例（84%），FMF-组146例（16%），两组患者临床表现及治疗反应的患病率差异有统计学意义。最后一次随访时，433例（50.6%）患者仍有一些疾病活动。在最后一次随访中，749例（85.5%）患者服用了秋水仙碱，但剂量相对不足。133例患者（15.2%）接受了抗il -1治疗，主要是canakinumab（117例，13.4%）。治疗依从性一般令人满意，不良事件一般轻微。结论缺乏基因证实的fmf样表型患者在临床特征和发作时间上存在显著差异，在病程中对治疗反应较差，应考虑为fmf样表型患者，并调查其他原因。纵向数据对FMF的长期负担以及治疗对疾病活动和患者生活质量的影响提供了更详细的理解。

{"title":"Long-term efficacy and safety of colchicine and anti-IL-1 blockers in FMF: results from the Eurofever multicenter observational study","authors":"Marta Bustaffa , Saverio La Bella , Yagmur Bayindir , Gayane Amaryan , Romina Gallizzi , Efimia Papadopoulou-Alataki , Giovanna Fabio , Naiera Assalia , Gil Amarilyo , Sevcan Bakkaloglu , Milos Jesenak , Luciana Breda , Jordi Anton , Elizabeth Legger , Maria Alessio , Gabriele Simonini , Donato Rigante , Laura Obici , Jasmin Kuemmerle-Deschner , Ozgur Kasapcopur , Seza Ozen","doi":"10.1016/j.jaut.2025.103421","DOIUrl":"10.1016/j.jaut.2025.103421","url":null,"abstract":"<div><h3>Introduction</h3><div>The majority of currently available data on familial Mediterranean fever (FMF) come from retrospective national or international studies.</div></div><div><h3>Methods</h3><div>An observational study collected data on the Eurofever international FMF cohort. Patients fulfilling genetic and clinical Eurofever criteria were considered as FMF+. Patients not fulfilling clinical and/or genetic (one VUS or benign variants or negative for <em>MEFV</em> variants) criteria were considered as FMF-. Data on compliance to treatment and quality of life were also recorded.</div></div><div><h3>Results</h3><div>Since November 2024, 876 FMF patients (466 M, 410 F) were enrolled, with a mean follow-up of 2.9 ± 3.1 years. 730 (84 %) patients were classified as FMF+, 146 (16 %) as FMF-, with significant differences in the prevalence of clinical manifestations and treatment response between the two groups. At the last follow-up, 433 patients (50.6 %) still had some disease activity. At the last follow-up 749 (85.5 %) patients received colchicine with a relative under dosage of the drug. Anti-IL-1 treatment was reported in 133 patients (15.2 %), mostly canakinumab (117, 13.4 %). Treatment compliance was generally satisfactory, and adverse events were generally mild.</div></div><div><h3>Conclusions</h3><div>Patients with an FMF-like phenotype who lack genetic confirmation display significant differences in clinical features and duration of attacks and show a less response to treatment during their disease course in respect, and thus, should be considered as FMF-mimics and investigated for other causes. Longitudinal data provides a more detailed comprehension of the long-term burden of FMF and the impact of treatment on disease activity and patients' quality of life.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103421"},"PeriodicalIF":7.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Treatment of uveitis in Blau syndrome: A systematic review and meta-analysis Blau综合征葡萄膜炎的治疗：系统回顾和荟萃分析

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1016/j.jaut.2025.103401

Ilaria Maccora , Carine Wouters , Carlos D. Rosè , Valerio Maniscalco , Salvatore de Masi , Maria Vincenza Mastrolia , Edoardo Marrani , Ilaria Pagnini , Gabriele Simonini

Objectives

Blau syndrome (BS) is a rare autoinflammatory disease caused by gain of function variants in NOD2. Uveitis is one of the triad features with arthritis and dermatitis. Management of uveitis is challenging, and uncontrolled uveitis may lead to blindness. We aim to evaluate the evidence regarding effectiveness of systemic treatments, including conventional Disease Modifying anti-Rheumatic drugs(cDMARDs) and biologic DMARDs(bDMARDs), for the management of uveitis in BS.

Methods

A systematic literature review and meta-analysis was performed according to PRISMA guidelines. Papers were selected if they reported patients with BS and uveitis who received systemic treatment. Papers were selected if reporting efficacy according to Standardization of Uveitis Nomenclature (SUN) criteria.

Results

We identified 1205 papers with 11 selected for systematic review and meta-analysis. Among the 11 selected papers, we identified 88 treatments. Among these, 53 were cDMARDs (36 methotrexate, 7 azathioprine, 5 mycophenolate, 3 thalidomide, 1 tacrolimus and 1 cyclosporine) and 35 bDMARDs (23 adalimumab, 6 infliximab, 4 etanercept, 1 golimumab and 1 canakinumab). The proportion of children showing improvement of uveitis was 20 % (95 % CI 2–46) and 22 % (95 % CI3-47) for cDMARDs and bDMARDs respectively (χ²0.23, p = 0.631). No differences were observed among the administered drugs (χ²7.21, p = 0.706).

Conclusion

The data show that there is not enough evidence to establish a preferred treatment for managing uveitis in BS. Considering the rarity, the potential severity and refractoriness to current treatments of the disease, there is a critical need for better understanding of pathophysiology and expert driven treatment guidelines for of BS-uveitis.

目的blau综合征（BS）是一种罕见的由NOD2功能变异获得引起的自身炎症性疾病。葡萄膜炎是关节炎和皮炎的三联征之一。葡萄膜炎的治疗具有挑战性，不受控制的葡萄膜炎可能导致失明。我们的目标是评估系统性治疗的有效性证据，包括传统的疾病修饰抗风湿药物（cDMARDs）和生物DMARDs(bDMARDs)，用于治疗BS患者的葡萄膜炎。方法根据PRISMA指南进行系统文献综述和meta分析。报道BS和葡萄膜炎患者接受全身治疗的论文入选。根据葡萄膜炎命名法标准化（SUN）标准选择报告疗效的论文。结果共纳入1205篇论文，其中11篇入选系统评价和荟萃分析。在入选的11篇论文中，我们确定了88种治疗方法。其中，cdmard 53个（甲氨喋呤36个，硫唑嘌呤7个，霉酚酸酯5个，沙利度胺3个，他克莫司1个，环孢素1个），bdmard 35个（阿达木单抗23个，英夫利昔单抗6个，依那西普4个，戈利姆单抗1个，canakinumab 1个）。cDMARDs患儿葡萄膜炎改善的比例为20% (95% CI 2-46)， bDMARDs患儿葡萄膜炎改善的比例为22% (95% CI3-47) （χ20.23, p = 0.631）。各给药组间差异无统计学意义（χ27.21, p = 0.706）。结论没有足够的证据来确定治疗BS患者葡萄膜炎的首选治疗方法。考虑到这种疾病的罕见性、潜在的严重性和目前治疗方法的难治性，迫切需要更好地了解bs -葡萄膜炎的病理生理学和专家驱动的治疗指南。

{"title":"Treatment of uveitis in Blau syndrome: A systematic review and meta-analysis","authors":"Ilaria Maccora , Carine Wouters , Carlos D. Rosè , Valerio Maniscalco , Salvatore de Masi , Maria Vincenza Mastrolia , Edoardo Marrani , Ilaria Pagnini , Gabriele Simonini","doi":"10.1016/j.jaut.2025.103401","DOIUrl":"10.1016/j.jaut.2025.103401","url":null,"abstract":"<div><h3>Objectives</h3><div>Blau syndrome (BS) is a rare autoinflammatory disease caused by gain of function variants in NOD2. Uveitis is one of the triad features with arthritis and dermatitis. Management of uveitis is challenging, and uncontrolled uveitis may lead to blindness. We aim to evaluate the evidence regarding effectiveness of systemic treatments, including conventional Disease Modifying anti-Rheumatic drugs(cDMARDs) and biologic DMARDs(bDMARDs), for the management of uveitis in BS.</div></div><div><h3>Methods</h3><div>A systematic literature review and meta-analysis was performed according to PRISMA guidelines. Papers were selected if they reported patients with BS and uveitis who received systemic treatment. Papers were selected if reporting efficacy according to Standardization of Uveitis Nomenclature (SUN) criteria.</div></div><div><h3>Results</h3><div>We identified 1205 papers with 11 selected for systematic review and meta-analysis. Among the 11 selected papers, we identified 88 treatments. Among these, 53 were cDMARDs (36 methotrexate, 7 azathioprine, 5 mycophenolate, 3 thalidomide, 1 tacrolimus and 1 cyclosporine) and 35 bDMARDs (23 adalimumab, 6 infliximab, 4 etanercept, 1 golimumab and 1 canakinumab). The proportion of children showing improvement of uveitis was 20 % (95 % CI 2–46) and 22 % (95 % CI3-47) for cDMARDs and bDMARDs respectively (χ<sup>2</sup>0.23, p = 0.631). No differences were observed among the administered drugs (χ<sup>2</sup>7.21, p = 0.706).</div></div><div><h3>Conclusion</h3><div>The data show that there is not enough evidence to establish a preferred treatment for managing uveitis in BS. Considering the rarity, the potential severity and refractoriness to current treatments of the disease, there is a critical need for better understanding of pathophysiology and expert driven treatment guidelines for of BS-uveitis.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103401"},"PeriodicalIF":7.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Neutrophil extracellular traps induce trophoblasts pyroptosis via enhancing NLRP3 lactylation in SLE pregnancies 中性粒细胞胞外陷阱通过增强NLRP3乳酸化诱导SLE妊娠滋养细胞热亡

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-05-01 Epub Date: 2025-04-03 DOI: 10.1016/j.jaut.2025.103411

Haoyue Hu , You Peng , Chi Chiu Wang , Jun Chen , Xiao Yu , Xiaoyan Chen , Haotong Ouyang , Qin Huang , Jing Ma , Qian Yin , Lien Ma , Ziling Ding , Minyi Zhang , Hao Ren , Jiaman Zheng , Wenqian Chen , Zixin Tao , Ruiyan Liu , Lu Chen , Xuefei Wang , Mei Zhong

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder primarily affecting women during the reproductive years, often complicating pregnancy outcomes with elevated levels of neutrophil extracellular traps (NETs) infiltration. However, potential impacts of NETs on placental trophoblasts in SLE and the underlying molecular mechanisms remain unclear. To address this, transcriptome sequencing was conducted on placentas collected from seven pregnant women with SLE and six healthy pregnant controls to identify SLE-specific placental features. The effects of NETs were further assessed in MRL/lpr lupus-prone mice and pristane-induced lupus (PIL) mice, focusing on pregnancy outcomes and placental pathology. In vitro, trophoblasts were stimulated with NETs derived from patients with SLE, followed by molecular analyses such as transcriptomic, cellular energy metabolism assays and liquid chromatography-tandem mass spectrometry to explore the effects and mechanisms of NETs. Results showed elevated NETs were observed in the placentas of both patients with SLE and lupus mouse models, accompanied by activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. Treatment with DNase I significantly improved pregnancy outcomes in MRL/lpr mice, while the use of peptidyl arginine deiminase 4 (PAD4)-deficient mice was beneficial on the pregnancy outcomes of PIL mice. Furthermore, SLE-derived NETs activated pyroptosis in trophoblasts by promoting glycolysis and subsequent lactylation of NLRP3. These findings highlight that NETs contribute to placental damage in SLE by inducing the lactylation of the NLRP3 inflammasome in trophoblasts, demonstrating the therapeutic potential of inhibiting NETs to improve placental function.

系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，主要影响育龄期妇女，通常伴有中性粒细胞胞外陷阱（NETs）浸润水平升高，使妊娠结局复杂化。然而，NETs对SLE中胎盘滋养细胞的潜在影响及其潜在的分子机制尚不清楚。为了解决这个问题，研究人员对7名SLE孕妇和6名健康孕妇的胎盘进行了转录组测序，以确定SLE特异性胎盘特征。在MRL/lpr狼疮易感小鼠和前列腺素诱导狼疮（PIL）小鼠中进一步评估NETs的作用，重点关注妊娠结局和胎盘病理。在体外，用SLE患者的NETs刺激滋养细胞，然后通过转录组学、细胞能量代谢测定和液相色谱-串联质谱等分子分析来探索NETs的作用和机制。结果显示，SLE和狼疮小鼠模型的胎盘中均观察到NETs升高，并伴有NOD-、LRR-和pyrin结构域蛋白3 （NLRP3）炎症小体的激活。DNase I治疗可显著改善MRL/lpr小鼠的妊娠结局，而使用肽基精氨酸脱亚胺酶4 （PAD4）缺陷小鼠对PIL小鼠的妊娠结局有益。此外，sled衍生的NETs通过促进NLRP3的糖酵解和随后的乳酸化，激活滋养层细胞的焦亡。这些发现强调，NETs通过诱导滋养细胞NLRP3炎性体的乳酸化而导致SLE的胎盘损伤，证明了抑制NETs改善胎盘功能的治疗潜力。

{"title":"Neutrophil extracellular traps induce trophoblasts pyroptosis via enhancing NLRP3 lactylation in SLE pregnancies","authors":"Haoyue Hu , You Peng , Chi Chiu Wang , Jun Chen , Xiao Yu , Xiaoyan Chen , Haotong Ouyang , Qin Huang , Jing Ma , Qian Yin , Lien Ma , Ziling Ding , Minyi Zhang , Hao Ren , Jiaman Zheng , Wenqian Chen , Zixin Tao , Ruiyan Liu , Lu Chen , Xuefei Wang , Mei Zhong","doi":"10.1016/j.jaut.2025.103411","DOIUrl":"10.1016/j.jaut.2025.103411","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder primarily affecting women during the reproductive years, often complicating pregnancy outcomes with elevated levels of neutrophil extracellular traps (NETs) infiltration. However, potential impacts of NETs on placental trophoblasts in SLE and the underlying molecular mechanisms remain unclear. To address this, transcriptome sequencing was conducted on placentas collected from seven pregnant women with SLE and six healthy pregnant controls to identify SLE-specific placental features. The effects of NETs were further assessed in MRL/lpr lupus-prone mice and pristane-induced lupus (PIL) mice, focusing on pregnancy outcomes and placental pathology. <em>In vitro,</em> trophoblasts were stimulated with NETs derived from patients with SLE, followed by molecular analyses such as transcriptomic, cellular energy metabolism assays and liquid chromatography-tandem mass spectrometry to explore the effects and mechanisms of NETs. Results showed elevated NETs were observed in the placentas of both patients with SLE and lupus mouse models, accompanied by activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. Treatment with DNase I significantly improved pregnancy outcomes in MRL/lpr mice, while the use of peptidyl arginine deiminase 4 (PAD4)-deficient mice was beneficial on the pregnancy outcomes of PIL mice. Furthermore, SLE-derived NETs activated pyroptosis in trophoblasts by promoting glycolysis and subsequent lactylation of NLRP3. These findings highlight that NETs contribute to placental damage in SLE by inducing the lactylation of the NLRP3 inflammasome in trophoblasts, demonstrating the therapeutic potential of inhibiting NETs to improve placental function.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103411"},"PeriodicalIF":7.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Exploring the correlation between UVB sensitivity and SLE activity: Insights into UVB-driven pathogenesis in lupus erythematosus 探索UVB敏感性与SLE活动的相关性：对UVB驱动的红斑狼疮发病机制的见解

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity

Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1016/j.jaut.2025.103393

Jiayu He , Yuanning Guo , Jiamin Chen , Jinhua Xu , Xiaohua Zhu

Lupus erythematosus (LE) comprises various autoimmune inflammatory diseases, with significant overlap between cutaneous LE (CLE) and systemic LE (SLE). A key feature of both CLE and SLE is UV photosensitivity, particularly in UV-exposure-related skin inflammation. Despite this, reliable and objective UVB photosensitivity indicators closely correlating with LE activity have yet to be identified, and the underlying cellular and molecular mechanisms linking UVB sensitivity with LE onset and progression remain unclear.

We discovered that ultraviolet B minimal erythema dose (UVB-MED), a quantitative photosensitivity measure, is a significant and independent risk factor for SLE activity, demonstrating a negative correlation with SLEDAI (r = −0.58, P < 0.0001). Comprehensive transcriptomic analyses of large-scale CLE and SLE samples (5918 in discovery and 7242 in validation datasets) revealed more pronounced and extensive UVB-response gene dysregulation in skin tissues compared to blood. Additionally, 14 lupus activity-correlated, UVB-response genes (UVBACGs) were identified, including eight type I interferon-stimulated genes (IRF7, ISG20, ISG15, IFI44, IFITM1, MX1, LY6E, OASL) and others (JUN, PTTG1, HLA-F, CAV1, HOPX, RPL3), with dysregulation evident in skin, blood, and affected organs (e.g., kidney and synovium). Immunocytes serve as the primary carriers of this dysregulation. Conventional LE therapies and type I interferon-targeted therapies were found to be associated with these genes and can potentially regulate them, thereby contributing to therapeutic effects.

These findings highlight the role of UVB in triggering autoimmune inflammation in the skin, which may subsequently spread to systemic inflammation via immune cells and factors. UVBACGs play a critical role in this process and may serve as targets for precise therapies, providing insight into the link between UVB photosensitivity and LE pathogenesis.

红斑狼疮（Lupus erythematosus， LE）包括多种自身免疫性炎症性疾病，皮肤性红斑狼疮（CLE）和系统性红斑狼疮（SLE）之间有明显的重叠。CLE和SLE的一个关键特征是紫外线光敏性，特别是与紫外线暴露相关的皮肤炎症。尽管如此，与LE活性密切相关的可靠和客观的UVB光敏指标尚未确定，并且将UVB敏感性与LE发生和进展联系起来的潜在细胞和分子机制仍不清楚。我们发现紫外线B最小红斑剂量（UVB-MED），一种定量光敏测量，是SLE活动的一个重要和独立的危险因素，与SLEDAI呈负相关(r = - 0.58, P <；0.0001)。对大规模CLE和SLE样本（发现5918例，验证数据集7242例）的综合转录组学分析显示，与血液相比，皮肤组织中uvb反应基因失调更为明显和广泛。此外，我们还发现了14个与狼疮活动相关的uhbv应答基因（UVBACGs），包括8个I型干扰素刺激基因（IRF7、ISG20、ISG15、IFI44、IFITM1、MX1、LY6E、OASL）和其他基因（JUN、PTTG1、HLA-F、CAV1、HOPX、RPL3），在皮肤、血液和受影响器官（如肾脏和滑膜）中存在明显的失调。免疫细胞是这种失调的主要载体。常规LE治疗和I型干扰素靶向治疗被发现与这些基因相关，并可能调节它们，从而有助于治疗效果。这些发现强调了UVB在触发皮肤自身免疫性炎症中的作用，这种炎症可能随后通过免疫细胞和因子扩散到全身炎症。UVBACGs在这一过程中发挥着关键作用，可能作为精确治疗的靶点，为了解UVB光敏性与LE发病机制之间的联系提供了线索。

{"title":"Exploring the correlation between UVB sensitivity and SLE activity: Insights into UVB-driven pathogenesis in lupus erythematosus","authors":"Jiayu He , Yuanning Guo , Jiamin Chen , Jinhua Xu , Xiaohua Zhu","doi":"10.1016/j.jaut.2025.103393","DOIUrl":"10.1016/j.jaut.2025.103393","url":null,"abstract":"<div><div>Lupus erythematosus (LE) comprises various autoimmune inflammatory diseases, with significant overlap between cutaneous LE (CLE) and systemic LE (SLE). A key feature of both CLE and SLE is UV photosensitivity, particularly in UV-exposure-related skin inflammation. Despite this, reliable and objective UVB photosensitivity indicators closely correlating with LE activity have yet to be identified, and the underlying cellular and molecular mechanisms linking UVB sensitivity with LE onset and progression remain unclear.</div><div>We discovered that ultraviolet B minimal erythema dose (UVB-MED), a quantitative photosensitivity measure, is a significant and independent risk factor for SLE activity, demonstrating a negative correlation with SLEDAI (r = −0.58, <em>P</em> < 0.0001). Comprehensive transcriptomic analyses of large-scale CLE and SLE samples (5918 in discovery and 7242 in validation datasets) revealed more pronounced and extensive UVB-response gene dysregulation in skin tissues compared to blood. Additionally, 14 lupus activity-correlated, UVB-response genes (UVBACGs) were identified, including eight type I interferon-stimulated genes (IRF7, ISG20, ISG15, IFI44, IFITM1, MX1, LY6E, OASL) and others (JUN, PTTG1, HLA-F, CAV1, HOPX, RPL3), with dysregulation evident in skin, blood, and affected organs (e.g., kidney and synovium). Immunocytes serve as the primary carriers of this dysregulation. Conventional LE therapies and type I interferon-targeted therapies were found to be associated with these genes and can potentially regulate them, thereby contributing to therapeutic effects.</div><div>These findings highlight the role of UVB in triggering autoimmune inflammation in the skin, which may subsequently spread to systemic inflammation via immune cells and factors. UVBACGs play a critical role in this process and may serve as targets for precise therapies, providing insight into the link between UVB photosensitivity and LE pathogenesis.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103393"},"PeriodicalIF":7.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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