Pub Date : 2025-04-15DOI: 10.1016/j.jaut.2025.103417
Shintaro Shirahama , Yoko Okunuki , May Y. Lee , Margarete M. Karg , Nasrin Refaian , Drenushe Krasniqi , Kip M. Connor , Meredith S. Gregory-Ksander , Bruce R. Ksander
Autoimmune uveitis is a major cause of blindness and experimental autoimmune uveitis (EAU) is mediated by interphotoreceptor retinoid-binding protein specific effector CD4+ T cells that infiltrate the retina. At least two MHC Class II (MHC II) antigen-presenting cell (APC) events are required for uveitis to develop. The first occurs in the secondary lymphoid organs when dendritic cells (DCs) activate and expand effector CD4+ T cells that enter the circulation and migrate systemically. The second APC event occurs when DC-primed effector CD4+ T cells infiltrate the retina and are restimulated by the relevant autoantigen. Importantly, if this second restimulation does not occur, then uveitis does not develop. However, it is still unclear which cell type(s) function as APCs within the retina. There are two candidate MHC II+ cell types-resident microglia and infiltrating DCs. We used the inducible Cre-lox approach to develop mouse strains in which MHC II was knocked out specifically on microglia using either the P2ry12 or Tmem119 gene to drive recombination. We also used Itgax (CD11c encoding gene) to drive recombination in DCs. Using this approach, we uncovered that the second APC event was mediated by MHC II+ microglia and not infiltrating MHC II+ DCs. Therefore, microglia are an important therapeutic target that can prevent and/or diminish uveitis even in the presence of circulating retinal autoantigen-specific effector CD4+ T cells.
{"title":"Preventing the antigen-presenting function of retinal microglia blocks autoimmune neuroinflammation by dendritic cell-primed CD4+ T cells","authors":"Shintaro Shirahama , Yoko Okunuki , May Y. Lee , Margarete M. Karg , Nasrin Refaian , Drenushe Krasniqi , Kip M. Connor , Meredith S. Gregory-Ksander , Bruce R. Ksander","doi":"10.1016/j.jaut.2025.103417","DOIUrl":"10.1016/j.jaut.2025.103417","url":null,"abstract":"<div><div>Autoimmune uveitis is a major cause of blindness and experimental autoimmune uveitis (EAU) is mediated by interphotoreceptor retinoid-binding protein specific effector CD4<sup>+</sup> T cells that infiltrate the retina. At least two MHC Class II (MHC II) antigen-presenting cell (APC) events are required for uveitis to develop. The first occurs in the secondary lymphoid organs when dendritic cells (DCs) activate and expand effector CD4<sup>+</sup> T cells that enter the circulation and migrate systemically. The second APC event occurs when DC-primed effector CD4<sup>+</sup> T cells infiltrate the retina and are restimulated by the relevant autoantigen. Importantly, if this second restimulation does not occur, then uveitis does not develop. However, it is still unclear which cell type(s) function as APCs within the retina. There are two candidate MHC II<sup>+</sup> cell types-resident microglia and infiltrating DCs. We used the inducible Cre-lox approach to develop mouse strains in which MHC II was knocked out specifically on microglia using either the <em>P2ry12</em> or <em>Tmem119</em> gene to drive recombination. We also used <em>Itgax</em> (CD11c encoding gene) to drive recombination in DCs. Using this approach, we uncovered that the second APC event was mediated by MHC II<sup>+</sup> microglia and not infiltrating MHC II<sup>+</sup> DCs. Therefore, microglia are an important therapeutic target that can prevent and/or diminish uveitis even in the presence of circulating retinal autoantigen-specific effector CD4<sup>+</sup> T cells.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103417"},"PeriodicalIF":7.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834429","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}
Pub Date : 2025-04-08DOI: 10.1016/j.jaut.2025.103416
Annalisa Marino , Irene Genovali , Luca Navarini , Elena Pontarini , Marta Vomero , Damiano Currado , Andrea Pilato , Letizia Pia Di Corcia , Michele Bombardieri , Roberto Giacomelli , Onorina Berardicurti
Sjögren's disease is a systemic autoimmune disease that primarily affects the exocrine glands, causing the main symptoms of xerostomia and xerophthalmia. In about half of the patients, it also causes systemic symptoms, which can potentially involve any organ or system. To date, the management of these patients is particularly complex due to the lack of recognized and approved therapies for the disease, except for medications used as symptomatic treatment for dryness. Due to the limited evidence available, therapeutic decisions in daily practice are frequently based on a combination of expert opinions and personal experience, which can vary significantly between clinicians. On these bases, we performed as systematic literature review critically analyzing the results of the previous trials, unpacking the single domains of ESSDAI, to evaluate if there are treatments significantly effective in some manifestations of the disease.
{"title":"Clinical targeted treatment in Sjogren's disease: A systematic literature review for an evidence-based medicine approach","authors":"Annalisa Marino , Irene Genovali , Luca Navarini , Elena Pontarini , Marta Vomero , Damiano Currado , Andrea Pilato , Letizia Pia Di Corcia , Michele Bombardieri , Roberto Giacomelli , Onorina Berardicurti","doi":"10.1016/j.jaut.2025.103416","DOIUrl":"10.1016/j.jaut.2025.103416","url":null,"abstract":"<div><div>Sjögren's disease is a systemic autoimmune disease that primarily affects the exocrine glands, causing the main symptoms of xerostomia and xerophthalmia. In about half of the patients, it also causes systemic symptoms, which can potentially involve any organ or system. To date, the management of these patients is particularly complex due to the lack of recognized and approved therapies for the disease, except for medications used as symptomatic treatment for dryness. Due to the limited evidence available, therapeutic decisions in daily practice are frequently based on a combination of expert opinions and personal experience, which can vary significantly between clinicians. On these bases, we performed as systematic literature review critically analyzing the results of the previous trials, unpacking the single domains of ESSDAI, to evaluate if there are treatments significantly effective in some manifestations of the disease.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103416"},"PeriodicalIF":7.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792079","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}
Pub Date : 2025-04-03DOI: 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.
{"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":"2025-04-03","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}
Labial salivary glands (LSG) from Sjögren's disease (SjD) patients are characterized by increased levels of pro-inflammatory cytokines, such as type I interferons (IFN-I). These LSG also show activation of the integrated stress response (ISR) with overexpression of protein kinase R (PKR), a known IFN-stimulated gene. In vitro, IFN-I stimulation reproduces the downregulation of hsa-miR-145-5p, which is associated with TLR4 overexpression observed in LSG of SjD patients. MicroRNA levels depend on its biogenesis, which is a multi-step process involving several protein complexes. It is not known whether altered miRNA biogenesis is associated with the activation of the ISR induced by IFN-I in LSG from SjD. The aim of this study was to characterize the expression and localization of components of the miRNA biogenesis machinery in LSG of SjD patients, to assess the effect of pro-inflammatory cytokines on these components, and to test whether inhibition of the IFN-β-induced ISR restores the levels of hsa-miR-145-5p. In LSG from 12 SjD patients and 11 non-SjD sicca controls, we determined mRNA fold changes, relative protein levels, and the localization of the ISR and miRNA biogenesis machinery components by RT-qPCR, Western blot, and immunofluorescence, respectively. Pro-inflammatory cytokines, the ISR inhibitor ISRIB, and the PKR inhibitor C16 were used for in vitro assays. In LSG from SjD patients, PKR and its activator PACT colocalized in the cytoplasm, whereas the PKR inhibitor TRBP was observed in the nuclei. IFN-β activates PKR, increases p-eIF2α and ATF4 levels, and increases PACT and AGO2 detection in stress granules. C16 inhibits PKR phosphorylation but increases ATF4 by activating GCN2. ISRIB restores levels of hsa-miR-145-5p and its target TLR4 mRNA upon IFN-β stimulation. These findings suggest an association between inflammation, cellular stress, and miRNA biogenesis, where modulation of the ISR emerges as a potential strategy to restore cellular homeostasis in LSG from SjD patients.
{"title":"Integrated stress response inhibition restores hsa-miR-145-5p levels after IFN-β stimulation in salivary gland epithelial cells. Association between cellular stress and miRNA biogenesis in Sjögren's disease","authors":"Isabel Castro , Patricia Carvajal , Sergio Aguilera , María-José Barrera , Soledad Matus , Sergio González , Claudio Molina , María-Julieta González","doi":"10.1016/j.jaut.2025.103412","DOIUrl":"10.1016/j.jaut.2025.103412","url":null,"abstract":"<div><div>Labial salivary glands (LSG) from Sjögren's disease (SjD) patients are characterized by increased levels of pro-inflammatory cytokines, such as type I interferons (IFN-I). These LSG also show activation of the integrated stress response (ISR) with overexpression of protein kinase R (PKR), a known IFN-stimulated gene. <em>In vitro</em>, IFN-I stimulation reproduces the downregulation of hsa-miR-145-5p, which is associated with TLR4 overexpression observed in LSG of SjD patients. MicroRNA levels depend on its biogenesis, which is a multi-step process involving several protein complexes. It is not known whether altered miRNA biogenesis is associated with the activation of the ISR induced by IFN-I in LSG from SjD. The aim of this study was to characterize the expression and localization of components of the miRNA biogenesis machinery in LSG of SjD patients, to assess the effect of pro-inflammatory cytokines on these components, and to test whether inhibition of the IFN-β-induced ISR restores the levels of hsa-miR-145-5p. In LSG from 12 SjD patients and 11 non-SjD sicca controls, we determined mRNA fold changes, relative protein levels, and the localization of the ISR and miRNA biogenesis machinery components by RT-qPCR, Western blot, and immunofluorescence, respectively. Pro-inflammatory cytokines, the ISR inhibitor ISRIB, and the PKR inhibitor C16 were used for <em>in vitro</em> assays. In LSG from SjD patients, PKR and its activator PACT colocalized in the cytoplasm, whereas the PKR inhibitor TRBP was observed in the nuclei. IFN-β activates PKR, increases p-eIF2α and ATF4 levels, and increases PACT and AGO2 detection in stress granules. C16 inhibits PKR phosphorylation but increases ATF4 by activating GCN2. ISRIB restores levels of hsa-miR-145-5p and its target TLR4 mRNA upon IFN-β stimulation. These findings suggest an association between inflammation, cellular stress, and miRNA biogenesis, where modulation of the ISR emerges as a potential strategy to restore cellular homeostasis in LSG from SjD patients.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103412"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748148","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}
Pub Date : 2025-04-01DOI: 10.1016/j.jaut.2025.103414
Yuanyuan Yang , Wencong Liu , Zechang Zhang , Yujia zhang , Xuebin Wang , Jing Wang , Huaifang Cai , Yichan Liu , Ran Meng , Yuqi Fu , Hongmin Luo , Lei Yang , Wenxuan Liu
Background
Glucagon-like peptide-1 receptor (GLP-1R) agonists are emerging with therapeutic agents for the treatment of two of the most prevalent metabolic disorders: diabetes and obesity. However, the causal relationship between GLP-1R agonists and autoimmune diseases is still unclear.
Methods
The available cis-eQTLs for drug target genes (GLP-1Rs) were used as proxies for exposure to GLP-1R agonists. Obesity and type 2 diabetes mellitus (T2DM) were used as positive controls to ensure the reliability of the genetic instrument. Mendelian randomization (MR) was performed to reveal the causal association of genetic proxy GLP-1R agonists with 18 autoimmune diseases from the IEU OpenGwas database and FinnGen database. Finally, the results of the two databases were analyzed via meta-analysis.
Results
A total of 22 significant cis-eQTL single-nucleotide polymorphisms were included as genetic instruments. Positive control analysis revealed that GLP-1R agonists were significantly associated with obesity (OR = 0.826, p = 0.021) and T2DM (OR = 0.886, p < 0.001), which is consistent with the meta-analysis. MR analysis revealed that increased expression of the GLP-1R gene has a significant protective effect on type 1 diabetes mellitus (T1DM), hypothyroidism, primary biliary cholangitis (PBC) and rheumatoid arthritis (RA). However, the MR analysis suggested that increased expression of GLP-1R agonists may increase the risk of Graves' disease (GD), ulcerative colitis (UC) and psoriasis. Our findings were consistent with those of the meta-analysis.
Conclusions
This study provides new insights into potential adjuvant treatments for autoimmune diseases from the perspective of genetic variation and provides evidence for the safety of GLP-1R agonists.
胰高血糖素样肽-1受体（GLP-1R）激动剂正在作为治疗药物出现，用于治疗两种最常见的代谢紊乱：糖尿病和肥胖。然而，GLP-1R激动剂与自身免疫性疾病之间的因果关系尚不清楚。方法利用现有的药物靶基因（GLP-1Rs）顺式等位基因（cis- eqtl）作为GLP-1R激动剂暴露的指标。为确保遗传仪器的可靠性，以肥胖和2型糖尿病（T2DM）为阳性对照。采用孟德尔随机化（MR）来揭示遗传代理GLP-1R激动剂与来自IEU OpenGwas数据库和FinnGen数据库的18种自身免疫性疾病的因果关系。最后，对两个数据库的结果进行meta分析。结果共纳入22个显著的顺式eqtl单核苷酸多态性作为遗传工具。阳性对照分析显示，GLP-1R激动剂与肥胖（OR = 0.826, p = 0.021）和2型糖尿病(OR = 0.886, p <；0.001)，这与meta分析一致。MR分析显示，GLP-1R基因表达增加对1型糖尿病（T1DM）、甲状腺功能减退、原发性胆管炎（PBC）和类风湿性关节炎（RA）具有显著的保护作用。然而，MR分析表明，GLP-1R激动剂的表达增加可能增加Graves病（GD）、溃疡性结肠炎（UC）和牛皮癣的风险。我们的发现与meta分析的结果一致。结论本研究从遗传变异的角度为自身免疫性疾病的潜在辅助治疗提供了新的见解，为GLP-1R激动剂的安全性提供了证据。
{"title":"Exploring glucagon-like peptide-1 receptor agonists as potential disease-modifying agents in autoimmune diseases","authors":"Yuanyuan Yang , Wencong Liu , Zechang Zhang , Yujia zhang , Xuebin Wang , Jing Wang , Huaifang Cai , Yichan Liu , Ran Meng , Yuqi Fu , Hongmin Luo , Lei Yang , Wenxuan Liu","doi":"10.1016/j.jaut.2025.103414","DOIUrl":"10.1016/j.jaut.2025.103414","url":null,"abstract":"<div><h3>Background</h3><div>Glucagon-like peptide-1 receptor (GLP-1R) agonists are emerging with therapeutic agents for the treatment of two of the most prevalent metabolic disorders: diabetes and obesity. However, the causal relationship between GLP-1R agonists and autoimmune diseases is still unclear.</div></div><div><h3>Methods</h3><div>The available cis-eQTLs for drug target genes (GLP-1Rs) were used as proxies for exposure to GLP-1R agonists. Obesity and type 2 diabetes mellitus (T2DM) were used as positive controls to ensure the reliability of the genetic instrument. Mendelian randomization (MR) was performed to reveal the causal association of genetic proxy GLP-1R agonists with 18 autoimmune diseases from the IEU OpenGwas database and FinnGen database. Finally, the results of the two databases were analyzed via meta-analysis.</div></div><div><h3>Results</h3><div>A total of 22 significant cis-eQTL single-nucleotide polymorphisms were included as genetic instruments. Positive control analysis revealed that GLP-1R agonists were significantly associated with obesity (OR = 0.826, <em>p</em> = 0.021) and T2DM (OR = 0.886, <em>p</em> < 0.001), which is consistent with the meta-analysis. MR analysis revealed that increased expression of the GLP-1R gene has a significant protective effect on type 1 diabetes mellitus (T1DM), hypothyroidism, primary biliary cholangitis (PBC) and rheumatoid arthritis (RA). However, the MR analysis suggested that increased expression of GLP-1R agonists may increase the risk of Graves' disease (GD), ulcerative colitis (UC) and psoriasis. Our findings were consistent with those of the meta-analysis.</div></div><div><h3>Conclusions</h3><div>This study provides new insights into potential adjuvant treatments for autoimmune diseases from the perspective of genetic variation and provides evidence for the safety of GLP-1R agonists.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103414"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739157","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}
Pub Date : 2025-03-31DOI: 10.1016/j.jaut.2025.103413
Marie Beaufrère , Manon Jacoutot , Roula Said Nahal , Gina Cosentino , Tom Hutteau-Hamel , Gaelle Clavel , Aude Jobart Malfait , Luiza M. Araujo , Maxime Breban , Simon Glatigny
Objective
Spondyloarthritis (SpA) is a group of chronic inflammatory disorders associated with the human leukocyte antigen (HLA) class I allele HLA-B27. Transgenic rats expressing HLA-B27 and human β2-microglobulin (B27 rats) develop clinical manifestations resembling SpA called rat SpA. IL-17 and TNF are key proinflammatory cytokines implicated in both human and rat SpA. We aimed to determine which T cell subset(s) produce IL-17 and TNF during rat SpA, characterize their tissue distribution and tested their pathogenicity in vivo.
Methods
Cytokine production by T cell subsets was evaluated in target tissues and lymphoid organs during rat SpA. Pathogenicity of purified IL-17+ cells was assessed in vivo by cell transfer. Blood samples were used to translate B27 rats findings to SpA patients.
Results
Conventional CD4+ T cells (Foxp3-; Tconv) and γδ T cells were the main producers of both IL-17 and TNF in B27 rats. IL-17-producing Tconv and γδ T cells were expanded in the colon of premorbid 3-weeks-old B27 rats. C-C motif chemokine receptor 6 (CCR6) allowed the isolation of IL-17+ Tconv (Th17) in rat. Transfer of B27 rat IL-17-producing CCR6+ Tconv but not of γδ T cells into disease-free nude B27 rats induced arthritis, directly demonstrating for the first time the arthritogenic potential of Th17 cells in SpA. Finally, a CCR6+ IL-17+ Tconv expansion enriched for IL-17F production was evidenced in SpA patients.
Conclusion
Our study demonstrates that IL-17+TNF+CCR6+ Th17 cells and IL-17+ γδ T cells are expanded preceding SpA onset in B27 rats and that only IL-17+TNF+CCR6+ Th17 cells can trigger arthritis.
{"title":"Interleukin 17-producing C-C motif chemokine receptor 6 + conventional CD4+ T cells are arthritogenic in an animal model of spondyloarthritis","authors":"Marie Beaufrère , Manon Jacoutot , Roula Said Nahal , Gina Cosentino , Tom Hutteau-Hamel , Gaelle Clavel , Aude Jobart Malfait , Luiza M. Araujo , Maxime Breban , Simon Glatigny","doi":"10.1016/j.jaut.2025.103413","DOIUrl":"10.1016/j.jaut.2025.103413","url":null,"abstract":"<div><h3>Objective</h3><div>Spondyloarthritis (SpA) is a group of chronic inflammatory disorders associated with the human leukocyte antigen (HLA) class I allele HLA-B27. Transgenic rats expressing HLA-B27 and human β2-microglobulin (B27 rats) develop clinical manifestations resembling SpA called rat SpA. IL-17 and TNF are key proinflammatory cytokines implicated in both human and rat SpA. We aimed to determine which T cell subset(s) produce IL-17 and TNF during rat SpA, characterize their tissue distribution and tested their pathogenicity <em>in vivo</em>.</div></div><div><h3>Methods</h3><div>Cytokine production by T cell subsets was evaluated in target tissues and lymphoid organs during rat SpA. Pathogenicity of purified IL-17<sup>+</sup> cells was assessed <em>in vivo</em> by cell transfer. Blood samples were used to translate B27 rats findings to SpA patients.</div></div><div><h3>Results</h3><div>Conventional CD4<sup>+</sup> T cells (Foxp3<sup>-</sup>; Tconv) and γδ T cells were the main producers of both IL-17 and TNF in B27 rats. IL-17-producing Tconv and γδ T cells were expanded in the colon of premorbid 3-weeks-old B27 rats. C-C motif chemokine receptor 6 (CCR6) allowed the isolation of IL-17<sup>+</sup> Tconv (Th17) in rat. Transfer of B27 rat IL-17-producing CCR6<sup>+</sup> Tconv but not of γδ T cells into disease-free nude B27 rats induced arthritis, directly demonstrating for the first time the arthritogenic potential of Th17 cells in SpA. Finally, a CCR6<sup>+</sup> IL-17<sup>+</sup> Tconv expansion enriched for IL-17F production was evidenced in SpA patients.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that IL-17<sup>+</sup>TNF<sup>+</sup>CCR6<sup>+</sup> Th17 cells and IL-17<sup>+</sup> γδ T cells are expanded preceding SpA onset in B27 rats and that only IL-17<sup>+</sup>TNF<sup>+</sup>CCR6<sup>+</sup> Th17 cells can trigger arthritis.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103413"},"PeriodicalIF":7.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739134","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}
Pub Date : 2025-03-30DOI: 10.1016/j.jaut.2025.103410
James J. Knox, Jean L. Scholz, Hannah Futeran, Sofia Cataliotti, Michael P. Cancro
Objective
B cell ablation strategies show promise for treating humoral autoimmune diseases, but their impact on pathogenic tissue-localized T-bet+CD11c+ age-associated B cells (ABCs) is poorly defined. We assessed whether mAb-mediated B cell depletion impacts ABCs and other splenic B cell subsets in two mouse models of lupus.
Methods
Following disease onset, we injected NZBxNZWF1 mice (NZBWF1; n = 72) or bm12 chronic graft versus host disease mice (cGVHD; n = 59) with 0.2 mg or 1 mg of anti-BLyS (10F4), anti-CD20 (18B12), combined treatment, or saline. Spleens were harvested after two weeks and B cell subset representation was analyzed via flow cytometry.
Results
In the NZBWF1 model, lymphopenia and resistance to 10F4 and 18B12 that arose concomitant with disease onset complicated interpretation, as ablative activity was partial and variable in the follicular (FO) and marginal zone (MZ) pools. Conversely, the T-bet+CD11c+ ABC pool was unchanged or enlarged versus controls and was entirely refractory to antibody treatments. In the cGVHD model, both 10F4 and 18B12 treatments ablated nearly all FO B cells. MZ B cells were profoundly ablated by 10F4 but spared by 18B12 treatment, whereas 10F4 treatment spared a small, undefined subset of splenic B cells that was ablated by 18B12. In contrast, T-bet+CD11c+ ABCs were minimally impacted by either reagent alone or combined, regardless of dose.
Conclusion
The spleen-resident T-bet+CD11c+ ABC pool resists anti-BLyS and anti-CD20 ablative treatment. These findings have implications for antibody-mediated ablative strategies in patients with autoimmune diseases.
{"title":"T-bet+CD11c+ age-associated B cells resist BLyS- and CD20-targeted ablation in murine lupus models","authors":"James J. Knox, Jean L. Scholz, Hannah Futeran, Sofia Cataliotti, Michael P. Cancro","doi":"10.1016/j.jaut.2025.103410","DOIUrl":"10.1016/j.jaut.2025.103410","url":null,"abstract":"<div><h3>Objective</h3><div>B cell ablation strategies show promise for treating humoral autoimmune diseases, but their impact on pathogenic tissue-localized T-bet<sup>+</sup>CD11c<sup>+</sup> age-associated B cells (ABCs) is poorly defined. We assessed whether mAb-mediated B cell depletion impacts ABCs and other splenic B cell subsets in two mouse models of lupus.</div></div><div><h3>Methods</h3><div>Following disease onset, we injected NZBxNZWF1 mice (NZBWF1; n = 72) or bm12 chronic graft versus host disease mice (cGVHD; n = 59) with 0.2 mg or 1 mg of anti-BLyS (10F4), anti-CD20 (18B12), combined treatment, or saline. Spleens were harvested after two weeks and B cell subset representation was analyzed via flow cytometry.</div></div><div><h3>Results</h3><div>In the NZBWF1 model, lymphopenia and resistance to 10F4 and 18B12 that arose concomitant with disease onset complicated interpretation, as ablative activity was partial and variable in the follicular (FO) and marginal zone (MZ) pools. Conversely, the T-bet<sup>+</sup>CD11c<sup>+</sup> ABC pool was unchanged or enlarged versus controls and was entirely refractory to antibody treatments. In the cGVHD model, both 10F4 and 18B12 treatments ablated nearly all FO B cells. MZ B cells were profoundly ablated by 10F4 but spared by 18B12 treatment, whereas 10F4 treatment spared a small, undefined subset of splenic B cells that was ablated by 18B12. In contrast, T-bet<sup>+</sup>CD11c<sup>+</sup> ABCs were minimally impacted by either reagent alone or combined, regardless of dose.</div></div><div><h3>Conclusion</h3><div>The spleen-resident T-bet<sup>+</sup>CD11c<sup>+</sup> ABC pool resists anti-BLyS and anti-CD20 ablative treatment. These findings have implications for antibody-mediated ablative strategies in patients with autoimmune diseases.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103410"},"PeriodicalIF":7.9,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734951","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}
Desquamative interstitial pneumonia (DIP), a rare type of idiopathic interstitial pneumonia (IIP), is smoking-related. However, some cases of DIP can also occur in non-smokers with autoimmune disorders. The diagnosis of DIP requires an invasive surgical lung biopsy, therefore, identifying a non-invasive diagnostic biomarker for DIP is crucial. This study aimed to elucidate autoantibodies specific for DIP and evaluate their diagnostic utility. Autoantibodies in the sera of patients with DIP were screened using immunoprecipitation. The common proteins recognized by autoantibodies in patients with DIP were identified using mass spectrometry and enzyme-linked immunosorbent assay (ELISA), and compared to other types of interstitial lung diseases (ILD) and pulmonary diseases. Several characteristic proteins commonly recognized by the sera of patients with DIP were revealed using immunoprecipitation and these proteins were identified as annexin A (ANXA) proteins using mass spectrometry. Using ELISA, autoantibodies to several ANXA were detected more frequently and specifically in DIP compared with those with other types of ILDs and pulmonary diseases. In particular, anti-ANXA4 antibodies had a sensitivity of 52.6 % and specificity of 99 % for DIP compared with those of other types of ILD. Therefore, anti-ANXAs antibodies, especially anti-ANXA4, could be a candidate diagnostic biomarker for DIP.
{"title":"Anti-annexin A4 antibody as a biomarker for desquamative interstitial pneumonia","authors":"Noriho Sakamoto , Minoru Satoh , Kaname Ohyama , Nozomi Aibara , Yasuhiko Yamano , Yasuhiro Kondoh , Shimpei Morimoto , Mari Yamasue , Kosaku Komiya , Yoshiaki Kinoshita , Hiroshi Ishii , Masaki Fujita , Shigehisa Yanagi , Toshimasa Shimizu , Kiyoyasu Fukushima , Yoshiko Akiyama , Ritsuko Murakami , Takatomo Tokito , Daisuke Okuno , Mutsumi Ozasa , Hiroshi Mukae","doi":"10.1016/j.jaut.2025.103409","DOIUrl":"10.1016/j.jaut.2025.103409","url":null,"abstract":"<div><div>Desquamative interstitial pneumonia (DIP), a rare type of idiopathic interstitial pneumonia (IIP), is smoking-related. However, some cases of DIP can also occur in non-smokers with autoimmune disorders. The diagnosis of DIP requires an invasive surgical lung biopsy, therefore, identifying a non-invasive diagnostic biomarker for DIP is crucial. This study aimed to elucidate autoantibodies specific for DIP and evaluate their diagnostic utility. Autoantibodies in the sera of patients with DIP were screened using immunoprecipitation. The common proteins recognized by autoantibodies in patients with DIP were identified using mass spectrometry and enzyme-linked immunosorbent assay (ELISA), and compared to other types of interstitial lung diseases (ILD) and pulmonary diseases. Several characteristic proteins commonly recognized by the sera of patients with DIP were revealed using immunoprecipitation and these proteins were identified as annexin A (ANXA) proteins using mass spectrometry. Using ELISA, autoantibodies to several ANXA were detected more frequently and specifically in DIP compared with those with other types of ILDs and pulmonary diseases. In particular, anti-ANXA4 antibodies had a sensitivity of 52.6 % and specificity of 99 % for DIP compared with those of other types of ILD. Therefore, anti-ANXAs antibodies, especially anti-ANXA4, could be a candidate diagnostic biomarker for DIP.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"153 ","pages":"Article 103409"},"PeriodicalIF":7.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725504","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}
Pub Date : 2025-03-26DOI: 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":"2025-03-26","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}
Pub Date : 2025-03-26DOI: 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":"2025-03-26","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号