James J. Knox, Jean L. Scholz, Hannah Futeran, Sofia Cataliotti, Michael P. Cancro
{"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}
{"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}
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
{"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}
Ilaria Maccora , Carine Wouters , Carlos D. Rosè , Valerio Maniscalco , Salvatore de Masi , Maria Vincenza Mastrolia , Edoardo Marrani , Ilaria Pagnini , Gabriele Simonini
{"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}
{"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}
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
{"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}
Carmen Noelker , Florian Seitz , Annekathrin Sturn , Frauke Neff , Luminita-Cornelia Andrei-Selmer , Lorenz Rau , Armin Geyer , J. Alexander Ross , Michael Bacher , Richard Dodel
{"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}
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
{"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}
Steven Dang , Joan Wither , Igor Jurisica , Vinod Chandran , Lihi Eder
{"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}
Benjamin Chaigne , Alexandre Bense , Frédérique Aubourg , Christian Agard , Yannick Allanore , Alice Berezne , Grégory Pugnet , Eric Hachulla , Vincent Cottin , Arnaud Hot , Bertrand Dunogue , Anuxcy Kanagaratnam , Sylvain Palat , Alain Lescoat , Sabine Berthier , Emmanuel Chatelus , Sébastien Rivière , David Launay , Marie-Elise Truchetet , Anh Tuan Dinh-Xuan , Perrine Smets
{"title":"Total lung capacity is predictive of disease severity and survival in systemic sclerosis: A longitudinal analysis in 2347 patients from the French National Cohort Study","authors":"Benjamin Chaigne , Alexandre Bense , Frédérique Aubourg , Christian Agard , Yannick Allanore , Alice Berezne , Grégory Pugnet , Eric Hachulla , Vincent Cottin , Arnaud Hot , Bertrand Dunogue , Anuxcy Kanagaratnam , Sylvain Palat , Alain Lescoat , Sabine Berthier , Emmanuel Chatelus , Sébastien Rivière , David Launay , Marie-Elise Truchetet , Anh Tuan Dinh-Xuan , Perrine Smets","doi":"10.1016/j.jaut.2025.103391","DOIUrl":"10.1016/j.jaut.2025.103391","url":null,"abstract":"<div><h3>Background</h3><div>Total lung capacity (TLC) is seldom assessed in the prediction of systemic sclerosis (SSc) disease severity.</div></div><div><h3>Objective</h3><div>To describe and analyse TLC in SSc.</div></div><div><h3>Methods</h3><div>We performed a retrospective multicentre study of SSc patients enrolled in the French national SSc cohort with at least one TLC assessment, described patients based on baseline TLC measurements, modelized TLC trajectories in SSc, and associated TLC measures with disease prognosis.</div></div><div><h3>Results</h3><div>Two thousand three hundred and forty-seven patients were included in the study. Baseline TLC was associated with disease severity and survival, as well as with the occurrence of interstitial lung disease (ILD), lung fibrosis (LF), and pulmonary arterial hypertension (PAH). Individual TLC trajectories varied among patients. Different models of TLC trajectories were assessed using latent process mixed models. The best model showed that the vast majority of SSc patients had stable TLC trajectories and clustered patients into three groups predictive of SSc survival, ILD, LF, and PAH. Lastly, a 10 % decrease of TLC was found to be predictive of a 5 % decrease in forced vital capacity (FVC), a 10 % decrease in DLCO, and consequently an earlier predictive marker of ILD and LF than FVC.</div></div><div><h3>Limitations</h3><div>Retrospective study.</div></div><div><h3>Conclusion</h3><div>TLC is predictive of disease severity and survival in SSc and SSc-ILD. This work suggests TLC as an earlier risk factor for ILD and LF than FVC in SSc.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"152 ","pages":"Article 103391"},"PeriodicalIF":7.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535013","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}