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}
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":"2025-03-26","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}
Pub Date : 2025-03-01DOI: 10.1016/j.jaut.2025.103395
Shu Zhang , Qi Wen , Shengyao Su , Yaye Wang, Jingsi Wang, Nairong Xie, Wenjia Zhu, Xinmei Wen, Li Di, Yan Lu, Min Xu, Min Wang, Hai Chen, Jianying Duo, Yue Huang, Dongshan Wan, Zhen Tao, Shufang Zhao, Guoliang Chai, Junwei Hao, Yuwei Da
Background
Myasthenia gravis (MG) is an autoimmune neuromuscular disease marked by dysregulation of several immune cell populations. Here we explored peripheral immune landscape, particularly the role of low-density granulocytes (LDGs).
Methods
Single-cell and bulk RNA sequencing analyzed peripheral immune cells from MG patients pre- (n = 4) and after treatment (n = 2), as well as healthy controls (n = 3). Flow cytometry was employed for validating LDG subsets, and various functional assays were conducted to assess their impact on T cell proliferation and differentiation, NET formation, and ROS production.
Results
Single-cell analysis highlighted a shift towards inflammatory Th1/Th17/Tfh subsets, an intense interferon-mediated immune response, and an expansion of immature myeloid subsets in MG. Flow cytometry showed increased LDGs correlated with disease severity. Unlike myeloid-derived suppressor cells, MG LDGs do not restrict T cell proliferation but induce a pro-inflammatory Th1/Th17 response. They also display enhanced spontaneous neutrophil extracellular traps (NETs) formation and basal reactive oxygen species (ROS) production. LDGs decreased after intravenous immunoglobulin and increased after prolonged immunotherapy in minimal manifestation status (MM), with reduced pro-inflammatory activity. Bulk RNA sequencing revealed significant transcriptional differences in LDGs, especially in cell cycle and granule protein genes.
Conclusion
Peripheral immune profiling sheds light on the intricate role of LDGs in MG. These cells, as a distinct subtype of neutrophils with a proinflammatory phenotype, are notable increased in MG, exacerbating chronic inflammation. Furthermore, immunotherapy expanded LDGs but reduced their proinflammatory capacities. The complex interplay of LDGs in MG underscores their potential as biomarkers and therapeutic targets.
{"title":"Peripheral immune profiling highlights a dynamic role of low-density granulocytes in myasthenia gravis","authors":"Shu Zhang , Qi Wen , Shengyao Su , Yaye Wang, Jingsi Wang, Nairong Xie, Wenjia Zhu, Xinmei Wen, Li Di, Yan Lu, Min Xu, Min Wang, Hai Chen, Jianying Duo, Yue Huang, Dongshan Wan, Zhen Tao, Shufang Zhao, Guoliang Chai, Junwei Hao, Yuwei Da","doi":"10.1016/j.jaut.2025.103395","DOIUrl":"10.1016/j.jaut.2025.103395","url":null,"abstract":"<div><h3>Background</h3><div>Myasthenia gravis (MG) is an autoimmune neuromuscular disease marked by dysregulation of several immune cell populations. Here we explored peripheral immune landscape, particularly the role of low-density granulocytes (LDGs).</div></div><div><h3>Methods</h3><div>Single-cell and bulk RNA sequencing analyzed peripheral immune cells from MG patients pre- (n = 4) and after treatment (n = 2), as well as healthy controls (n = 3). Flow cytometry was employed for validating LDG subsets, and various functional assays were conducted to assess their impact on T cell proliferation and differentiation, NET formation, and ROS production.</div></div><div><h3>Results</h3><div>Single-cell analysis highlighted a shift towards inflammatory Th1/Th17/Tfh subsets, an intense interferon-mediated immune response, and an expansion of immature myeloid subsets in MG. Flow cytometry showed increased LDGs correlated with disease severity. Unlike myeloid-derived suppressor cells, MG LDGs do not restrict T cell proliferation but induce a pro-inflammatory Th1/Th17 response. They also display enhanced spontaneous neutrophil extracellular traps (NETs) formation and basal reactive oxygen species (ROS) production. LDGs decreased after intravenous immunoglobulin and increased after prolonged immunotherapy in minimal manifestation status (MM), with reduced pro-inflammatory activity. Bulk RNA sequencing revealed significant transcriptional differences in LDGs, especially in cell cycle and granule protein genes.</div></div><div><h3>Conclusion</h3><div>Peripheral immune profiling sheds light on the intricate role of LDGs in MG. These cells, as a distinct subtype of neutrophils with a proinflammatory phenotype, are notable increased in MG, exacerbating chronic inflammation. Furthermore, immunotherapy expanded LDGs but reduced their proinflammatory capacities. The complex interplay of LDGs in MG underscores their potential as biomarkers and therapeutic targets.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103395"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548998","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 : 2025-03-01DOI: 10.1016/j.jaut.2025.103392
Cailing Su , Ansheng Cong , Heng Wu , Zhanmei Zhou , Zuoyu Hu , Jiao Luo , Shuang Cui , Dongyan Xu , Zhuoyu Zhou , Zhijie Huang , Manqiu Yang , Guobao Wang , Wei Cao
Objective
Predictive models of kidney response to standard immunosuppression are needed in proliferative lupus nephritis (LN). We tested the kidney macrophage infiltration at initial biopsy.
Methods
The prospective study was performed in 247 patients with newly diagnosed proliferative LN in 2 independent cohorts. Infiltrates of macrophages and lymphocytes in initial biopsies were identified using single-cell RNA sequencing and immunostaining analysis. The outcome was kidney response to standard immunosuppression at 1 year, defined clinically and histologically. Kidney infiltrates were investigated for association with kidney response. Models that combined kidney infiltrates and clinical parameters for predicting kidney response were developed and validated using machine learning algorithms.
Results
In Derivation cohort, glomerular infiltration of CD68+ macrophages at initial biopsy was associated with 1-year clinical response. Subjects in the highest tertile of glomerular CD68+ macrophage infiltrate (versus the lowest) had a 7.92-fold increase in probability of clinical response. An intelligent model incorporating infiltration score of glomerular CD68+ macrophage into clinical measures (area under the curve [AUC] 0.82) outperformed traditional clinical measure-based model (AUC 0.76) in predicting clinical response (P = 0.01). This intelligent model performed well in an independent Validation cohort. Furthermore, in 10 patients undergoing repeat kidney biopsy after 1 year of standard immunosuppression, our intelligent model effectively predicted histological response.
Conclusion
Intensity of glomerular CD68+ macrophage infiltration at initial biopsy predicted 1-year kidney response to standard therapy in proliferative LN. The intelligent model, which combines glomerular CD68+ macrophage infiltrates with clinical data at biopsy, could help discriminate responders from non-responders, enabling personalized therapy.
{"title":"Glomerular CD68+ macrophages infiltration at initial biopsy predicts response to standard immunosuppression in proliferative lupus nephritis","authors":"Cailing Su , Ansheng Cong , Heng Wu , Zhanmei Zhou , Zuoyu Hu , Jiao Luo , Shuang Cui , Dongyan Xu , Zhuoyu Zhou , Zhijie Huang , Manqiu Yang , Guobao Wang , Wei Cao","doi":"10.1016/j.jaut.2025.103392","DOIUrl":"10.1016/j.jaut.2025.103392","url":null,"abstract":"<div><h3>Objective</h3><div>Predictive models of kidney response to standard immunosuppression are needed in proliferative lupus nephritis (LN). We tested the kidney macrophage infiltration at initial biopsy.</div></div><div><h3>Methods</h3><div>The prospective study was performed in 247 patients with newly diagnosed proliferative LN in 2 independent cohorts. Infiltrates of macrophages and lymphocytes in initial biopsies were identified using single-cell RNA sequencing and immunostaining analysis. The outcome was kidney response to standard immunosuppression at 1 year, defined clinically and histologically. Kidney infiltrates were investigated for association with kidney response. Models that combined kidney infiltrates and clinical parameters for predicting kidney response were developed and validated using machine learning algorithms.</div></div><div><h3>Results</h3><div>In Derivation cohort, glomerular infiltration of CD68<sup>+</sup> macrophages at initial biopsy was associated with 1-year clinical response. Subjects in the highest tertile of glomerular CD68<sup>+</sup> macrophage infiltrate (<em>versus</em> the lowest) had a 7.92-fold increase in probability of clinical response. An intelligent model incorporating infiltration score of glomerular CD68<sup>+</sup> macrophage into clinical measures (area under the curve [AUC] 0.82) outperformed traditional clinical measure-based model (AUC 0.76) in predicting clinical response (P = 0.01). This intelligent model performed well in an independent Validation cohort. Furthermore, in 10 patients undergoing repeat kidney biopsy after 1 year of standard immunosuppression, our intelligent model effectively predicted histological response.</div></div><div><h3>Conclusion</h3><div>Intensity of glomerular CD68<sup>+</sup> macrophage infiltration at initial biopsy predicted 1-year kidney response to standard therapy in proliferative LN. The intelligent model, which combines glomerular CD68<sup>+</sup> macrophage infiltrates with clinical data at biopsy, could help discriminate responders from non-responders, enabling personalized therapy.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103392"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519104","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 : 2025-03-01DOI: 10.1016/j.jaut.2025.103390
Carmen Noelker , Florian Seitz , Annekathrin Sturn , Frauke Neff , Luminita-Cornelia Andrei-Selmer , Lorenz Rau , Armin Geyer , J. Alexander Ross , Michael Bacher , Richard Dodel
Aggregates of α-synuclein (α-Syn) are the major component of the Lewy bodies associated with Parkinson's disease. Recently, naturally occurring autoantibodies against α-synuclein (α-Syn-nAbs) were detected. Herein we have isolated and further characterized such α-Syn-nAbs. Using an affinity column coated with α-Syn, we have isolated α-Syn-nAbs from a commercially available intravenous Immunoglobulin (IVIg) preparation. A methodological approach based on ELISA, Western blotting and immunoprecipitation as well as surface plasmon resonance, was used to determine binding capacity to α-Syn. The epitope was determined via peptide array membrane and the functionality was tested in vitro using a toxicity and a fibrillation assay. The autoantibodies display strong binding capacity to α-Syn as demonstrated by ELISA, immunoprecipitation and Western blotting analysis. The binding affinities of the purified autoantibodies were analyzed in detail by surface plasmon resonance (Biacore). The epitope on α-Syn that is recognized by the α-Syn nAbs was fully determined. A sequence within the non-amyloid component (NAC)-Region of α-Syn is crucial for the binding of α-Syn-nAbs to α-Syn. Furthermore, the α-Syn-nAbs had an inhibitory effect on α-Syn fibril formation and were also able to specifically reverse the toxicity of α-Syn oligomers species in human neuroblastoma (SH-SY5Y) cells. Our results emphasize the possible importance of naturally occurring autoantibodies for the pathogenesis of Parkinson's disease. Since autoantibodies against α-Syn are detectable in human serum and cerebrospinal fluid and interfere with pathological events associated with α-Syn, they may provide a candidate for the treatment of Parkinson's disease.
α-突触核蛋白（α-Syn）的聚集体是与帕金森病相关的路易体的主要成分。最近，自然产生的抗α-突触核蛋白自身抗体（α- syn - nab）被检测到。在此，我们分离并进一步表征了这种α- syn - nab。利用包被α-Syn的亲和柱，我们从市售的静脉注射免疫球蛋白（IVIg）制剂中分离出α-Syn- nab。采用ELISA、Western blotting、免疫沉淀、表面等离子体共振等方法测定α-Syn的结合能力。通过肽阵列膜确定表位，并使用体外毒性和纤颤试验测试其功能。ELISA、免疫沉淀和Western blotting分析表明，自身抗体对α-Syn具有较强的结合能力。用表面等离子体共振（Biacore）对纯化的自身抗体的结合亲和力进行了详细的分析。完全确定了α-Syn抗体识别的α-Syn表位。α-Syn的非淀粉样成分（NAC）区域内的序列对于α-Syn- nab与α-Syn的结合至关重要。此外，α-Syn- nab对α-Syn纤维的形成具有抑制作用，并且能够特异性逆转α-Syn低聚物物种对人神经母细胞瘤（SH-SY5Y）细胞的毒性。我们的结果强调了自然产生的自身抗体在帕金森病发病机制中的重要性。由于抗α-Syn的自身抗体在人血清和脑脊液中可检测到，并干扰与α-Syn相关的病理事件，因此它们可能为帕金森病的治疗提供候选药物。
{"title":"Autoantibodies against α-synuclein inhibit its aggregation and cytotoxicity","authors":"Carmen Noelker , Florian Seitz , Annekathrin Sturn , Frauke Neff , Luminita-Cornelia Andrei-Selmer , Lorenz Rau , Armin Geyer , J. Alexander Ross , Michael Bacher , Richard Dodel","doi":"10.1016/j.jaut.2025.103390","DOIUrl":"10.1016/j.jaut.2025.103390","url":null,"abstract":"<div><div>Aggregates of α-synuclein (α-Syn) are the major component of the Lewy bodies associated with Parkinson's disease. Recently, naturally occurring autoantibodies against α-synuclein (α-Syn-nAbs) were detected. Herein we have isolated and further characterized such α-Syn-nAbs. Using an affinity column coated with α-Syn, we have isolated α-Syn-nAbs from a commercially available intravenous Immunoglobulin (IVIg) preparation. A methodological approach based on ELISA, Western blotting and immunoprecipitation as well as surface plasmon resonance, was used to determine binding capacity to α-Syn. The epitope was determined via peptide array membrane and the functionality was tested <em>in vitro</em> using a toxicity and a fibrillation assay. The autoantibodies display strong binding capacity to α-Syn as demonstrated by ELISA, immunoprecipitation and Western blotting analysis. The binding affinities of the purified autoantibodies were analyzed in detail by surface plasmon resonance (Biacore). The epitope on α-Syn that is recognized by the α-Syn nAbs was fully determined. A sequence within the non-amyloid component (NAC)-Region of α-Syn is crucial for the binding of α-Syn-nAbs to α-Syn. Furthermore, the α-Syn-nAbs had an inhibitory effect on α-Syn fibril formation and were also able to specifically reverse the toxicity of α-Syn oligomers species in human neuroblastoma (SH-SY5Y) cells. Our results emphasize the possible importance of naturally occurring autoantibodies for the pathogenesis of Parkinson's disease. Since autoantibodies against α-Syn are detectable in human serum and cerebrospinal fluid and interfere with pathological events associated with α-Syn, they may provide a candidate for the treatment of Parkinson's disease.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103390"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535014","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 : 2025-03-01DOI: 10.1016/j.jaut.2025.103394
Steven Dang , Joan Wither , Igor Jurisica , Vinod Chandran , Lihi Eder
Psoriasis and spondyloarthritis (SpA), including psoriatic arthritis (PsA), are immune-mediated inflammatory conditions that affect the skin and musculoskeletal system. Males and female patients with psoriatic disease and SpA exhibit differences in clinical presentation, disease progression, and treatment response. The underlying biological mechanisms driving these sex differences remain poorly understood. This review explores the current evidence on sex-related differences in biomarkers and biological pathways in psoriasis, PsA, and SpA. While no conclusive sex-specific biomarkers have been validated, this review highlights several sex-related differences in biomarkers and biological pathways, including differences in bone turnover markers, IL-23/IL-17 pathway activity, pro-inflammatory cytokines, and cardio-metabolic profiles that may partially contribute to the clinical differences observed between male and female patients. Sex hormones may contribute to the altered bone metabolism and immune regulation in females. To effectively identify and validate sex-specific biomarkers, there is a need to prioritize sex as a biological variable in future research. Adopting such an approach should enhance more personalized therapeutic strategies and improve management for male and female patients with psoriatic disease and SpA.
{"title":"Sex differences in biomarkers and biologic mechanisms in psoriatic diseases and spondyloarthritis","authors":"Steven Dang , Joan Wither , Igor Jurisica , Vinod Chandran , Lihi Eder","doi":"10.1016/j.jaut.2025.103394","DOIUrl":"10.1016/j.jaut.2025.103394","url":null,"abstract":"<div><div>Psoriasis and spondyloarthritis (SpA), including psoriatic arthritis (PsA), are immune-mediated inflammatory conditions that affect the skin and musculoskeletal system. Males and female patients with psoriatic disease and SpA exhibit differences in clinical presentation, disease progression, and treatment response. The underlying biological mechanisms driving these sex differences remain poorly understood. This review explores the current evidence on sex-related differences in biomarkers and biological pathways in psoriasis, PsA, and SpA. While no conclusive sex-specific biomarkers have been validated, this review highlights several sex-related differences in biomarkers and biological pathways, including differences in bone turnover markers, IL-23/IL-17 pathway activity, pro-inflammatory cytokines, and cardio-metabolic profiles that may partially contribute to the clinical differences observed between male and female patients. Sex hormones may contribute to the altered bone metabolism and immune regulation in females. To effectively identify and validate sex-specific biomarkers, there is a need to prioritize sex as a biological variable in future research. Adopting such an approach should enhance more personalized therapeutic strategies and improve management for male and female patients with psoriatic disease and SpA.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103394"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527267","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}
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