Journal of autoimmunity最新文献

{"title":"Clinical targeted treatment in Sjogren's disease: A systematic literature review for an evidence-based medicine approach","authors":"Annalisa Marino ,&nbsp;Irene Genovali ,&nbsp;Luca Navarini ,&nbsp;Elena Pontarini ,&nbsp;Marta Vomero ,&nbsp;Damiano Currado ,&nbsp;Andrea Pilato ,&nbsp;Letizia Pia Di Corcia ,&nbsp;Michele Bombardieri ,&nbsp;Roberto Giacomelli ,&nbsp;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}

{"title":"Neutrophil extracellular traps induce trophoblasts pyroptosis via enhancing NLRP3 lactylation in SLE pregnancies","authors":"Haoyue Hu ,&nbsp;You Peng ,&nbsp;Chi Chiu Wang ,&nbsp;Jun Chen ,&nbsp;Xiao Yu ,&nbsp;Xiaoyan Chen ,&nbsp;Haotong Ouyang ,&nbsp;Qin Huang ,&nbsp;Jing Ma ,&nbsp;Qian Yin ,&nbsp;Lien Ma ,&nbsp;Ziling Ding ,&nbsp;Minyi Zhang ,&nbsp;Hao Ren ,&nbsp;Jiaman Zheng ,&nbsp;Wenqian Chen ,&nbsp;Zixin Tao ,&nbsp;Ruiyan Liu ,&nbsp;Lu Chen ,&nbsp;Xuefei Wang ,&nbsp;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}

{"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 ,&nbsp;Patricia Carvajal ,&nbsp;Sergio Aguilera ,&nbsp;María-José Barrera ,&nbsp;Soledad Matus ,&nbsp;Sergio González ,&nbsp;Claudio Molina ,&nbsp;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}

{"title":"Exploring glucagon-like peptide-1 receptor agonists as potential disease-modifying agents in autoimmune diseases","authors":"Yuanyuan Yang ,&nbsp;Wencong Liu ,&nbsp;Zechang Zhang ,&nbsp;Yujia zhang ,&nbsp;Xuebin Wang ,&nbsp;Jing Wang ,&nbsp;Huaifang Cai ,&nbsp;Yichan Liu ,&nbsp;Ran Meng ,&nbsp;Yuqi Fu ,&nbsp;Hongmin Luo ,&nbsp;Lei Yang ,&nbsp;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> &lt; 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}

{"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 ,&nbsp;Manon Jacoutot ,&nbsp;Roula Said Nahal ,&nbsp;Gina Cosentino ,&nbsp;Tom Hutteau-Hamel ,&nbsp;Gaelle Clavel ,&nbsp;Aude Jobart Malfait ,&nbsp;Luiza M. Araujo ,&nbsp;Maxime Breban ,&nbsp;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⁺ 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⁺ 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.</div></div><div><h3>Conclusion</h3><div>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.</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}

{"title":"T-bet+CD11c+ age-associated B cells resist BLyS- and CD20-targeted ablation in murine lupus models","authors":"James J. Knox,&nbsp;Jean L. Scholz,&nbsp;Hannah Futeran,&nbsp;Sofia Cataliotti,&nbsp;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⁺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.</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⁺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.</div></div><div><h3>Conclusion</h3><div>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.</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}

{"title":"Anti-annexin A4 antibody as a biomarker for desquamative interstitial pneumonia","authors":"Noriho Sakamoto ,&nbsp;Minoru Satoh ,&nbsp;Kaname Ohyama ,&nbsp;Nozomi Aibara ,&nbsp;Yasuhiko Yamano ,&nbsp;Yasuhiro Kondoh ,&nbsp;Shimpei Morimoto ,&nbsp;Mari Yamasue ,&nbsp;Kosaku Komiya ,&nbsp;Yoshiaki Kinoshita ,&nbsp;Hiroshi Ishii ,&nbsp;Masaki Fujita ,&nbsp;Shigehisa Yanagi ,&nbsp;Toshimasa Shimizu ,&nbsp;Kiyoyasu Fukushima ,&nbsp;Yoshiko Akiyama ,&nbsp;Ritsuko Murakami ,&nbsp;Takatomo Tokito ,&nbsp;Daisuke Okuno ,&nbsp;Mutsumi Ozasa ,&nbsp;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}

{"title":"Mepolizumab versus benralizumab for eosinophilic granulomatosis with polyangiitis (EGPA): A European real-life retrospective comparative study","authors":"Irene Mattioli ,&nbsp;Maria Letizia Urban ,&nbsp;Roberto Padoan ,&nbsp;Aladdin J. Mohammad ,&nbsp;Carlo Salvarani ,&nbsp;Chiara Baldini ,&nbsp;Alvise Berti ,&nbsp;Paolo Cameli ,&nbsp;Marco Caminati ,&nbsp;Pascal Cathébras ,&nbsp;Fulvia Chieco Bianchi ,&nbsp;Francesco Cinetto ,&nbsp;Jan Willem Cohen Tervaert ,&nbsp;Angelo Coppola ,&nbsp;Giulia Costanzo ,&nbsp;Vincent Cottin ,&nbsp;Claudia Crimi ,&nbsp;Stefano Del Giacco ,&nbsp;Charlene Desaintjean ,&nbsp;Allyson Egan ,&nbsp;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 &lt; 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}

{"title":"Treatment of uveitis in Blau syndrome: A systematic review and meta-analysis","authors":"Ilaria Maccora ,&nbsp;Carine Wouters ,&nbsp;Carlos D. Rosè ,&nbsp;Valerio Maniscalco ,&nbsp;Salvatore de Masi ,&nbsp;Maria Vincenza Mastrolia ,&nbsp;Edoardo Marrani ,&nbsp;Ilaria Pagnini ,&nbsp;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 (χ²0.23, p = 0.631). No differences were observed among the administered drugs (χ²7.21, 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}

{"title":"Exploring the correlation between UVB sensitivity and SLE activity: Insights into UVB-driven pathogenesis in lupus erythematosus","authors":"Jiayu He ,&nbsp;Yuanning Guo ,&nbsp;Jiamin Chen ,&nbsp;Jinhua Xu ,&nbsp;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> &lt; 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":"2025-03-26","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}