Pub Date : 2024-11-05DOI: 10.1186/s13075-024-03419-1
Stephanie L Smith, Lorna Paul, Martijn P M Steultjens, Rebecca L Jones
Objectives: Skeletal muscle dysfunction is the primary cause of functional limitations in osteoarthritis, associated biomarkers have the potential as targets for early disease identification, diagnosis, and prevention of osteoarthritis disability. This review aimed to identify associations between biomarkers and lower limb skeletal muscle function in individuals with osteoarthritis.
Methods: A systematic literature review and meta-analysis conducted in PubMed, MEDLINE, CINAHL, EMBASE, Scopus, SPORTDiscus and Web of Science databases from inception to 8th August 2023. Two independent reviewers performed the title, abstract, full-text screening, data extraction and methodological quality assessment. A meta-analysis was undertaken based on the available data.
Results: Twenty-four studies with 4101 participants with osteoarthritis were included (females: 78%; age range; 49 to 71 years). One study reported muscle-specific biomarkers (n = 3), whilst six studies reported osteoarthritis-specific markers (n = 5). Overall, 93 biomarkers were reported, predominately characterised as inflammatory (n = 35), metabolic (n = 15), and hormones (n = 10). Muscle strength and vitamin D reported a significant association (Hedge's g: 0.58 (Standard Error (SE): 0.27; P = 0.03), k = 3 studies). Walking speed and high-sensitivity C-reactive protein reported no significant associations (Hedge's g: -0.02 (SE: 0.05; P = 0.73), k = 3 studies).
Conclusion: Associations between biomarkers and lower limb skeletal muscle function in individuals with osteoarthritis was limited, the few studies exploring lower limb muscle measures were mainly secondary outcomes. Furthermore, biomarkers were largely related to overall health, with a lack of muscle specific biomarkers. As such, the mechanistic pathways through which these associations occur are less evident, and difficult to draw clear conclusions on these relationships.
Trial registration: Registered on PROSPERO (CRD42022359405).
目的：骨骼肌功能障碍是骨关节炎患者功能受限的主要原因，相关的生物标志物有可能成为早期疾病识别、诊断和预防骨关节炎残疾的目标。本综述旨在确定骨关节炎患者的生物标志物与下肢骨骼肌功能之间的关联：从开始到 2023 年 8 月 8 日，在 PubMed、MEDLINE、CINAHL、EMBASE、Scopus、SPORTDiscus 和 Web of Science 数据库中进行了系统的文献综述和荟萃分析。两位独立审稿人对论文标题、摘要、全文进行了筛选，并对数据提取和方法学质量进行了评估。根据现有数据进行了荟萃分析：结果：共纳入 24 项研究，4101 名骨关节炎患者参与了研究（女性：78%；年龄范围：49 岁至 71 岁）。一项研究报告了肌肉特异性生物标记物（n = 3），六项研究报告了骨关节炎特异性标记物（n = 5）。总体而言，共报告了 93 种生物标记物，主要分为炎症标记物（35 种）、代谢标记物（15 种）和激素标记物（10 种）。据报告，肌肉力量与维生素 D 有显著关联（Hedge's g：0.58（标准误差 (SE)：0.27；P = 0.03），k = 3 项研究）。步行速度与高敏 C 反应蛋白无明显关联（Hedge's g：-0.02 (SE: 0.05; P = 0.73)，k = 3 项研究）：结论：骨关节炎患者的生物标志物与下肢骨骼肌功能之间的关联有限，少数几项探讨下肢肌肉指标的研究主要是次要结果。此外，生物标志物主要与整体健康有关，缺乏肌肉特异性生物标志物。因此，发生这些关联的机理途径并不明显，也很难就这些关系得出明确的结论：注册于 PROSPERO（CRD42022359405）。
{"title":"Associations between biomarkers and skeletal muscle function in individuals with osteoarthritis: a systematic review and meta-analysis.","authors":"Stephanie L Smith, Lorna Paul, Martijn P M Steultjens, Rebecca L Jones","doi":"10.1186/s13075-024-03419-1","DOIUrl":"10.1186/s13075-024-03419-1","url":null,"abstract":"<p><strong>Objectives: </strong>Skeletal muscle dysfunction is the primary cause of functional limitations in osteoarthritis, associated biomarkers have the potential as targets for early disease identification, diagnosis, and prevention of osteoarthritis disability. This review aimed to identify associations between biomarkers and lower limb skeletal muscle function in individuals with osteoarthritis.</p><p><strong>Methods: </strong>A systematic literature review and meta-analysis conducted in PubMed, MEDLINE, CINAHL, EMBASE, Scopus, SPORTDiscus and Web of Science databases from inception to 8<sup>th</sup> August 2023. Two independent reviewers performed the title, abstract, full-text screening, data extraction and methodological quality assessment. A meta-analysis was undertaken based on the available data.</p><p><strong>Results: </strong>Twenty-four studies with 4101 participants with osteoarthritis were included (females: 78%; age range; 49 to 71 years). One study reported muscle-specific biomarkers (n = 3), whilst six studies reported osteoarthritis-specific markers (n = 5). Overall, 93 biomarkers were reported, predominately characterised as inflammatory (n = 35), metabolic (n = 15), and hormones (n = 10). Muscle strength and vitamin D reported a significant association (Hedge's g: 0.58 (Standard Error (SE): 0.27; P = 0.03), k = 3 studies). Walking speed and high-sensitivity C-reactive protein reported no significant associations (Hedge's g: -0.02 (SE: 0.05; P = 0.73), k = 3 studies).</p><p><strong>Conclusion: </strong>Associations between biomarkers and lower limb skeletal muscle function in individuals with osteoarthritis was limited, the few studies exploring lower limb muscle measures were mainly secondary outcomes. Furthermore, biomarkers were largely related to overall health, with a lack of muscle specific biomarkers. As such, the mechanistic pathways through which these associations occur are less evident, and difficult to draw clear conclusions on these relationships.</p><p><strong>Trial registration: </strong>Registered on PROSPERO (CRD42022359405).</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"189"},"PeriodicalIF":4.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Patients with rheumatoid arthritis (RA) commonly experience a high prevalence of multiple metabolic diseases (MD), leading to higher morbidity and premature mortality. Here, we aimed to investigate the pathogenesis of MD in RA patients (RA_MD) through an integrated multi-omics approach.
Methods: Fecal and blood samples were collected from a total of 181 subjects in this study for multi-omics analyses, including 16S rRNA and internally transcribed spacer (ITS) gene sequencing, metabolomics, transcriptomics, proteomics and phosphoproteomics. Spearman's correlation and protein-protein interaction networks were used to assess the multi-omics data correlations. The Least Absolute Shrinkage and Selection Operator (LASSO) machine learning algorithm were used to identify disease-specific biomarkers for RA_MD diagnosis.
Results: Our results found that RA_MD was associated with differential abundance of gut microbiota such as Turicibacter and Neocosmospora, metabolites including decreased unsaturated fatty acid, genes related to linoleic acid metabolism and arachidonic acid metabolism, as well as downregulation of proteins and phosphoproteins involved in cholesterol metabolism. Furthermore, a multi-omics classifier differentiated RA_MD from RA with high accuracy (AUC: 0.958). Compared to gouty arthritis and systemic lupus erythematosus, dysregulation of lipid metabolism showed disease-specificity in RA_MD.
Conclusions: The integration of multi-omics data demonstrates that lipid metabolic pathways play a crucial role in RA_MD, providing the basis and direction for the prevention and early diagnosis of MD, as well as new insights to complement clinical treatment options.
目的：类风湿性关节炎（RA）患者通常患有多种代谢性疾病（MD），导致发病率和死亡率升高。在此，我们旨在通过综合多组学方法研究 RA 患者（RA_MD）的 MD 发病机制：方法：本研究共收集了 181 名受试者的粪便和血液样本进行多组学分析，包括 16S rRNA 和内部转录间隔（ITS）基因测序、代谢组学、转录组学、蛋白质组学和磷酸化蛋白质组学。斯皮尔曼相关性和蛋白质-蛋白质相互作用网络用于评估多组学数据的相关性。使用最小绝对收缩和选择操作器（LASSO）机器学习算法来识别用于诊断RA_MD的疾病特异性生物标记物：我们的结果发现，RA_MD 与肠道微生物群（如 Turicibacter 和 Neocosmospora）的丰度差异、代谢物（包括不饱和脂肪酸的减少）、亚油酸代谢相关基因和花生四烯酸代谢相关基因以及参与胆固醇代谢的蛋白质和磷蛋白的下调有关。此外，多组学分类器还能准确地将 RA_MD 与 RA 区分开来（AUC：0.958）。与痛风性关节炎和系统性红斑狼疮相比，脂质代谢失调在RA_MD中表现出疾病特异性：多组学数据的整合表明，脂质代谢通路在RA_MD中起着至关重要的作用，为MD的预防和早期诊断提供了依据和方向，也为补充临床治疗方案提供了新的见解。
{"title":"Integrated multi-omics revealed that dysregulated lipid metabolism played an important role in RA patients with metabolic diseases.","authors":"Xiaoting Zhu, Wubin Long, Jing Zhang, Congcong Jian, Jianghua Chen, Jiaxin Huang, Shilin Li, Jie Zhang, Liang Wang, Yan Chen, Jianhong Wu, Tingting Wang, Qinghua Zou, Jing Zhu, Fanxin Zeng","doi":"10.1186/s13075-024-03423-5","DOIUrl":"10.1186/s13075-024-03423-5","url":null,"abstract":"<p><strong>Objectives: </strong>Patients with rheumatoid arthritis (RA) commonly experience a high prevalence of multiple metabolic diseases (MD), leading to higher morbidity and premature mortality. Here, we aimed to investigate the pathogenesis of MD in RA patients (RA_MD) through an integrated multi-omics approach.</p><p><strong>Methods: </strong>Fecal and blood samples were collected from a total of 181 subjects in this study for multi-omics analyses, including 16S rRNA and internally transcribed spacer (ITS) gene sequencing, metabolomics, transcriptomics, proteomics and phosphoproteomics. Spearman's correlation and protein-protein interaction networks were used to assess the multi-omics data correlations. The Least Absolute Shrinkage and Selection Operator (LASSO) machine learning algorithm were used to identify disease-specific biomarkers for RA_MD diagnosis.</p><p><strong>Results: </strong>Our results found that RA_MD was associated with differential abundance of gut microbiota such as Turicibacter and Neocosmospora, metabolites including decreased unsaturated fatty acid, genes related to linoleic acid metabolism and arachidonic acid metabolism, as well as downregulation of proteins and phosphoproteins involved in cholesterol metabolism. Furthermore, a multi-omics classifier differentiated RA_MD from RA with high accuracy (AUC: 0.958). Compared to gouty arthritis and systemic lupus erythematosus, dysregulation of lipid metabolism showed disease-specificity in RA_MD.</p><p><strong>Conclusions: </strong>The integration of multi-omics data demonstrates that lipid metabolic pathways play a crucial role in RA_MD, providing the basis and direction for the prevention and early diagnosis of MD, as well as new insights to complement clinical treatment options.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"188"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1186/s13075-024-03418-2
Anja Wyss, Suzana Jordan, Nicole Graf, Patricia E. Carreira, Jörg Distler, Marco Matucci Cerinic, Elise Siegert, Jörg Henes, Elisabetta Zanatta, Valeria Riccieri, Marie-Elise Truchetet, Fahrettin Oksel, Mengtao Li, Eugene J. Kucharz, Kilian Eyerich, Francesco Del Galdo, Madelon C. Vonk, Anna-Maria Hoffman Vold, Armando Gabrielli, Oliver Distler
Patients with diffuse cutaneous systemic sclerosis (dcSSc) frequently show spontaneous improvement of skin fibrosis. Our aim was to examine whether an improvement in skin fibrosis predicts lower likelihood of visceral organ progression and better survival. Patients from the European Scleroderma Trials and Research (EUSTAR) cohort with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, and valid mRSS at 12±3 months follow up were included. Regression/progression of skin fibrosis was defined as a decrease/increase in mRSS >5 points and ≥25% from baseline to follow up. The outcomes included progression of lung, renal, cardiac and gastrointestinal manifestations using consensus derived definitions and all-cause death. Regressive, stable and progressive patients were compared by univariate, Kaplan-Meier survival curve and Cox regression analysis. Of 1257 included patients, 883 (70.2%) were stable, 282 (22.4%) regressive, and 92 (7.3%) progressive. Regressive patients, adjusted for baseline mRSS, baseline immunosuppression, baseline FVC, and disease duration, showed a significantly lower probability of FVC decline ≥10% than progressive patients (p=0.00003), lower probability of all-cause mortality during follow up (p=0.035) compared to progressive patients. .Improvement of skin fibrosis was not associated with progression of other organ manifestations. We found that regression of skin fibrosis is associated with a lower probability of lung progression and better survival at follow up. The link between the disease course of skin and lung fibrosis in SSc can help to better stratify patients in clinical practice and enrich for ILD progressive patients in clinical trials. • Diffuse SSc patients with improvement of skin fibrosis had a lower probability of lung function progression and all-cause mortality than skin progressive patients. • This allows better risk stratification of SSc patients in clinical practice. • It could help to improve the design of clinical trials in SSc and better enrichment of ILD progressive patients.
{"title":"Does regression of skin thickening predict improvement of internal organ involvement and survival in patients with diffuse cutaneous systemic sclerosis? A EUSTAR analysis","authors":"Anja Wyss, Suzana Jordan, Nicole Graf, Patricia E. Carreira, Jörg Distler, Marco Matucci Cerinic, Elise Siegert, Jörg Henes, Elisabetta Zanatta, Valeria Riccieri, Marie-Elise Truchetet, Fahrettin Oksel, Mengtao Li, Eugene J. Kucharz, Kilian Eyerich, Francesco Del Galdo, Madelon C. Vonk, Anna-Maria Hoffman Vold, Armando Gabrielli, Oliver Distler","doi":"10.1186/s13075-024-03418-2","DOIUrl":"https://doi.org/10.1186/s13075-024-03418-2","url":null,"abstract":"Patients with diffuse cutaneous systemic sclerosis (dcSSc) frequently show spontaneous improvement of skin fibrosis. Our aim was to examine whether an improvement in skin fibrosis predicts lower likelihood of visceral organ progression and better survival. Patients from the European Scleroderma Trials and Research (EUSTAR) cohort with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, and valid mRSS at 12±3 months follow up were included. Regression/progression of skin fibrosis was defined as a decrease/increase in mRSS >5 points and\u0000≥25% from baseline to follow up. The outcomes included progression of lung, renal, cardiac and gastrointestinal manifestations using consensus derived definitions and all-cause death. Regressive, stable and progressive patients were compared by univariate, Kaplan-Meier survival curve and Cox regression analysis. Of 1257 included patients, 883 (70.2%) were stable, 282 (22.4%) regressive, and 92 (7.3%) progressive. Regressive patients, adjusted for baseline mRSS, baseline immunosuppression, baseline FVC, and disease duration, showed a significantly lower probability of FVC decline ≥10% than progressive patients (p=0.00003), lower probability of all-cause mortality during follow up (p=0.035) compared to progressive patients. .Improvement of skin fibrosis was not associated with progression of other organ manifestations. We found that regression of skin fibrosis is associated with a lower probability of lung progression and better survival at follow up. The link between the disease course of skin and lung fibrosis in SSc can help to better stratify patients in clinical practice and enrich for ILD progressive patients in clinical trials. • Diffuse SSc patients with improvement of skin fibrosis had a lower probability of lung function progression and all-cause mortality than skin progressive patients. • This allows better risk stratification of SSc patients in clinical practice. • It could help to improve the design of clinical trials in SSc and better enrichment of ILD progressive patients.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"131 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1186/s13075-024-03426-2
Jian Bin Li, Peng Cheng Liu, Liming Chen, Rui Wu
Objective: Rheumatoid arthritis (RA) is a clinically heterogeneous and complex autoimmune disease, making the prediction of therapeutic responses a significant challenge. This study aims to assess the role of clinical and synovial biomarkers in predicting poor response to adalimumab treatment in RA patients.
Methods: This single-center prospective study included 56 RA patients who had an inadequate response to methotrexate (MTX). At baseline, comprehensive assessments including complete blood count, liver and kidney function tests, blood glucose levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), as well as counts of swollen and tender joints, Health Assessment Questionnaire (HAQ) score, pain visual analogue scale (VAS) scores, and DAS28-CRP scores were conducted. Synovial biopsies were performed, followed by an efficacy evaluation at 12 weeks of adalimumab treatment. Patients not meeting the ACR20 criteria were classified into the non-responder group, with the remainder categorized as the responder group.
Results: Out of the participants, 24 (42.9%) failed to achieve ACR20 with adalimumab treatment. Non-responders exhibited higher infiltration of plasma cells in the synovium. Multivariate logistic regression analysis identified the presence of plasma cells as an independent risk factor for inadequate response to adalimumab.
Conclusion: Inadequate responses to adalimumab in RA patients were associated with increased plasma cell infiltrations in the synovium. These findings suggest a promising target for tailored therapies in rheumatoid arthritis.
{"title":"Infiltrations of plasma cells in synovium predict inadequate response to Adalimumab in Rheumatoid Arthritis patients.","authors":"Jian Bin Li, Peng Cheng Liu, Liming Chen, Rui Wu","doi":"10.1186/s13075-024-03426-2","DOIUrl":"10.1186/s13075-024-03426-2","url":null,"abstract":"<p><strong>Objective: </strong>Rheumatoid arthritis (RA) is a clinically heterogeneous and complex autoimmune disease, making the prediction of therapeutic responses a significant challenge. This study aims to assess the role of clinical and synovial biomarkers in predicting poor response to adalimumab treatment in RA patients.</p><p><strong>Methods: </strong>This single-center prospective study included 56 RA patients who had an inadequate response to methotrexate (MTX). At baseline, comprehensive assessments including complete blood count, liver and kidney function tests, blood glucose levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), as well as counts of swollen and tender joints, Health Assessment Questionnaire (HAQ) score, pain visual analogue scale (VAS) scores, and DAS28-CRP scores were conducted. Synovial biopsies were performed, followed by an efficacy evaluation at 12 weeks of adalimumab treatment. Patients not meeting the ACR20 criteria were classified into the non-responder group, with the remainder categorized as the responder group.</p><p><strong>Results: </strong>Out of the participants, 24 (42.9%) failed to achieve ACR20 with adalimumab treatment. Non-responders exhibited higher infiltration of plasma cells in the synovium. Multivariate logistic regression analysis identified the presence of plasma cells as an independent risk factor for inadequate response to adalimumab.</p><p><strong>Conclusion: </strong>Inadequate responses to adalimumab in RA patients were associated with increased plasma cell infiltrations in the synovium. These findings suggest a promising target for tailored therapies in rheumatoid arthritis.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":"186"},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1186/s13075-024-03422-6
Hui-Chun Yu, Hsien-Yu Huang Tseng, Hsien-Bin Huang, Ming-Chi Lu
To investigate the roles of Ca2+ influx-regulated circular RNAs (circRNAs) in T cells from patients with systemic lupus erythematosus (SLE). The expression profile of circRNAs in Jurkat cells, co-cultured with and without ionomycin, was analyzed by next-generation sequencing and validated using real-time polymerase chain reaction. The identified Ca2+ influx-regulated circRNAs were further examined in T cells from 42 patients with SLE and 23 healthy controls. The biological function of specific circRNA was investigated using transfection and RNA pull-down assay. After validation, we confirmed that the expression levels of circ-ERCC4, circ-NFATC2, circ-MYH10, circ-CAMTA1, circ-ASH1L, circ-SOCS7, and circ-ASAP1 were consistently increased in Jurkat cells following Ca2+ influx. The expression levels of circ-CAMTA1, circ-ASH1L, and circ-ASAP1 were significantly lower in T cells from patients with SLE, with even lower levels observed in those with higher disease activity. Interferon (IFN)-α was found to suppress the expression of circ-CAMTA1. Circ-CAMTA1 bound to pyruvate carboxylase and inhibited its biological activity. Overexpression of circ-CAMTA1, but not its linear form, significantly decreased extracellular glucose levels. Furthermore, increased expression of circ-CAMTA1, but not its linear form, decreased miR-181c-5p expression, resulting increased IL-2 secretion. Three Ca2+ influx-regulated circ-RNAs—circ-CAMTA1, circ-ASH1L, and circ-ASAP1 —were significantly reduced in T cells from patients with SLE and associated with disease activity. IFN-α suppressed the expression of circ-CAMTA1, which interacted with pyruvate carboxylase, inhibited its activity, affected glucose metabolism, and increased IL-2 secretion. These findings suggest that circ-CAMTA1 regulated by Ca²⁺ influx modulated T cell function in patients with SLE.
{"title":"Circ-CAMTA1 regulated by Ca2+ influx inhibited pyruvate carboxylase activity and modulate T cell function in patients with systemic lupus erythematosus","authors":"Hui-Chun Yu, Hsien-Yu Huang Tseng, Hsien-Bin Huang, Ming-Chi Lu","doi":"10.1186/s13075-024-03422-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03422-6","url":null,"abstract":"To investigate the roles of Ca2+ influx-regulated circular RNAs (circRNAs) in T cells from patients with systemic lupus erythematosus (SLE). The expression profile of circRNAs in Jurkat cells, co-cultured with and without ionomycin, was analyzed by next-generation sequencing and validated using real-time polymerase chain reaction. The identified Ca2+ influx-regulated circRNAs were further examined in T cells from 42 patients with SLE and 23 healthy controls. The biological function of specific circRNA was investigated using transfection and RNA pull-down assay. After validation, we confirmed that the expression levels of circ-ERCC4, circ-NFATC2, circ-MYH10, circ-CAMTA1, circ-ASH1L, circ-SOCS7, and circ-ASAP1 were consistently increased in Jurkat cells following Ca2+ influx. The expression levels of circ-CAMTA1, circ-ASH1L, and circ-ASAP1 were significantly lower in T cells from patients with SLE, with even lower levels observed in those with higher disease activity. Interferon (IFN)-α was found to suppress the expression of circ-CAMTA1. Circ-CAMTA1 bound to pyruvate carboxylase and inhibited its biological activity. Overexpression of circ-CAMTA1, but not its linear form, significantly decreased extracellular glucose levels. Furthermore, increased expression of circ-CAMTA1, but not its linear form, decreased miR-181c-5p expression, resulting increased IL-2 secretion. Three Ca2+ influx-regulated circ-RNAs—circ-CAMTA1, circ-ASH1L, and circ-ASAP1 —were significantly reduced in T cells from patients with SLE and associated with disease activity. IFN-α suppressed the expression of circ-CAMTA1, which interacted with pyruvate carboxylase, inhibited its activity, affected glucose metabolism, and increased IL-2 secretion. These findings suggest that circ-CAMTA1 regulated by Ca²⁺ influx modulated T cell function in patients with SLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1186/s13075-024-03415-5
Yuanyuan Niu, Suling Liu, Qian Qiu, Di Fu, Youjun Xiao, Liuqin Liang, Yang Cui, Shanhui Ye, Hanshi Xu
Anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5-positvie DM) is a subtype of dermatomyositis with a poor prognosis, characterized by rapidly progressive interstitial lung disease (RP-ILD). The study aims to investigate the significance of serum cytokines profiles and peripheral lymphocytes in predicting prognoses of anti-MDA5-positvie DM with RP-ILD. Furthermore, it seeks to analyze longitudinal data of lymphocytes during hospitalization to identify distinct trajectories and cluster patients accordingly. A total of 168 patients with anti-MDA5-positive DM were enrolled in this retrospective study from two cohorts. Univariate and multivariate Cox regression analyses were conducted to determine the predictors of 6-month all-cause mortality and RP-ILD. Group-based trajectory modeling (GBTM) was employed to model the trajectories of longitudinal peripheral lymphocytes. In the multivariate Cox regression analysis, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, lymphocytes from 0.5 to 1.0 × 109 /L, older age, and elevated LDH were identified as independent predictors of 6-month all-cause mortality. Furthermore, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, and lymphocytes from 0.5 to 1.0 × 109 /L were found to be independent predictors of RP-ILD. Additionally, three trajectory groups of lymphocytes within the first week after admission were established based on GBTM. These groups included: Group 1, with low-level of lymphocytes that declined; Group 2, with medium-level of lymphocytes that slightly rose; and Group 3, with high-level of lymphocytes that rose. Notably, group 1 showed the highest mortality (90.7%) and all experiencing RP-ILD. Increased expression of IL-6 in lung tissues was observed in two cases with RP-ILD compared to two cases without RP-ILD. We also found the increased infiltration of CD4 + and CD8 + T cells, particularly CD8 + T cells, in lung tissues from patients with RP-ILD. Our study demonstrated that increased level of serum IL-6 (≥ 13.41pg/mL) and severe lymphopenia were promising predictors of 6-month all-cause mortality and the occurrence of RP-ILD in anti-MDA5-positive DM patients. Furthermore, tracking distinct trajectories of lymphocytes during hospitalization can be utilized to cluster patients.
{"title":"Increased serum level of IL-6 predicts poor prognosis in anti-MDA5-positive dermatomyositis with rapidly progressive interstitial lung disease","authors":"Yuanyuan Niu, Suling Liu, Qian Qiu, Di Fu, Youjun Xiao, Liuqin Liang, Yang Cui, Shanhui Ye, Hanshi Xu","doi":"10.1186/s13075-024-03415-5","DOIUrl":"https://doi.org/10.1186/s13075-024-03415-5","url":null,"abstract":"Anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5-positvie DM) is a subtype of dermatomyositis with a poor prognosis, characterized by rapidly progressive interstitial lung disease (RP-ILD). The study aims to investigate the significance of serum cytokines profiles and peripheral lymphocytes in predicting prognoses of anti-MDA5-positvie DM with RP-ILD. Furthermore, it seeks to analyze longitudinal data of lymphocytes during hospitalization to identify distinct trajectories and cluster patients accordingly. A total of 168 patients with anti-MDA5-positive DM were enrolled in this retrospective study from two cohorts. Univariate and multivariate Cox regression analyses were conducted to determine the predictors of 6-month all-cause mortality and RP-ILD. Group-based trajectory modeling (GBTM) was employed to model the trajectories of longitudinal peripheral lymphocytes. In the multivariate Cox regression analysis, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, lymphocytes from 0.5 to 1.0 × 109 /L, older age, and elevated LDH were identified as independent predictors of 6-month all-cause mortality. Furthermore, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, and lymphocytes from 0.5 to 1.0 × 109 /L were found to be independent predictors of RP-ILD. Additionally, three trajectory groups of lymphocytes within the first week after admission were established based on GBTM. These groups included: Group 1, with low-level of lymphocytes that declined; Group 2, with medium-level of lymphocytes that slightly rose; and Group 3, with high-level of lymphocytes that rose. Notably, group 1 showed the highest mortality (90.7%) and all experiencing RP-ILD. Increased expression of IL-6 in lung tissues was observed in two cases with RP-ILD compared to two cases without RP-ILD. We also found the increased infiltration of CD4 + and CD8 + T cells, particularly CD8 + T cells, in lung tissues from patients with RP-ILD. Our study demonstrated that increased level of serum IL-6 (≥ 13.41pg/mL) and severe lymphopenia were promising predictors of 6-month all-cause mortality and the occurrence of RP-ILD in anti-MDA5-positive DM patients. Furthermore, tracking distinct trajectories of lymphocytes during hospitalization can be utilized to cluster patients.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"12 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1186/s13075-024-03408-4
Nicoletta Del Papa, Silvia Cavalli, Andrea Rindone, Francesco Onida, Giorgia Saporiti, Antonina Minniti, Maria Rosa Pellico, Claudia Iannone, Giorgia Trignani, Nicoletta D’Angelo, Manuel Sette, Raffaella Greco, Claudio Vitali, Roberto Caporali
Autologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT. Thirty-five dcSSc AHSCT-treated patients were compared with 29 and 36 matched cases treated with RTX and CIT, respectively. The patients were followed up for 5 years by assessing selected outcome measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC and DLCO), and the revised EUSTAR Activity Index (REAI) were the outcome measures chosen to evaluate the therapy efficacy. AHSCT was significantly more effective than RTX and CIT in prolonging survival, inducing a rapid reduction of the mRSS and REAI and maintaining the baseline level of lung function tests for a longer time. RTX therapy was also superior to CIT in reducing REAI, mRSS and in saving lung function. AHSCT is more effective than both RTX and CIT in prolonging survival and inducing prolonged remission in patients with rapidly progressive dcSSc.
{"title":"Long-term outcome of autologous haematopoietic stem cell transplantation in patients with systemic sclerosis: a comparison with patients treated with rituximab and with traditional immunosuppressive agents","authors":"Nicoletta Del Papa, Silvia Cavalli, Andrea Rindone, Francesco Onida, Giorgia Saporiti, Antonina Minniti, Maria Rosa Pellico, Claudia Iannone, Giorgia Trignani, Nicoletta D’Angelo, Manuel Sette, Raffaella Greco, Claudio Vitali, Roberto Caporali","doi":"10.1186/s13075-024-03408-4","DOIUrl":"https://doi.org/10.1186/s13075-024-03408-4","url":null,"abstract":"Autologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT. Thirty-five dcSSc AHSCT-treated patients were compared with 29 and 36 matched cases treated with RTX and CIT, respectively. The patients were followed up for 5 years by assessing selected outcome measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC and DLCO), and the revised EUSTAR Activity Index (REAI) were the outcome measures chosen to evaluate the therapy efficacy. AHSCT was significantly more effective than RTX and CIT in prolonging survival, inducing a rapid reduction of the mRSS and REAI and maintaining the baseline level of lung function tests for a longer time. RTX therapy was also superior to CIT in reducing REAI, mRSS and in saving lung function. AHSCT is more effective than both RTX and CIT in prolonging survival and inducing prolonged remission in patients with rapidly progressive dcSSc.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"62 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuropsychiatric systemic lupus erythematosus (NPSLE) often manifests as cognitive deterioration, with activated microglia and blood-brain barrier (BBB) disruption implicated in these neurological complications. Wnt-inhibitory factor-1 (WIF-1), a secreted protein, has been detected in the cerebrospinal fluid (CSF) of NPSLE patients. However, the contribution of WIF-1 in contributing to lupus cognitive impairment remains poorly understood. Using MRL/MpJ-Faslpr (MRL/lpr) lupus-prone mice and TLR7 agonist imiquimod (IMQ)-induced lupus mice, recombinant WIF-1 protein (rWIF-1) and adeno-associated virus (AAV) encoding sh-WIF-1 were administered via intracerebroventricular injection. Behavioral tests, histopathological examinations, flow cytometry, and molecular biology techniques were employed to investigate the underlying mechanisms. Microinjection of rWIF-1 exacerbated cognitive deficits and mood abnormalities, increased BBB leakage and neuronal degeneration, and caused aberrant activation of microglia and synaptic pruning in the hippocampus. Conversely, lupus mice injected with AAV-shWIF-1 exhibited significant remission. In vitro, rWIF-1 induced overactivation of microglia with an increased CD86+ pro-inflammatory subpopulation, upregulated phagocytic activity, and excessive synaptic engulfment, contributing to increased BBB permeability. Furthermore, WIF-1 exerted its biological effects through the CRYAB/STAT4 pathway, transcriptionally decreasing SHH production. We also identified that symmetric dimethylarginine (SDMA) could alleviate rWIF-1-induced microglial activation and BBB damage, thereby restoring SHH levels. In conclusion, WIF-1 exacerbates lupus-induced cognitive dysfunction in mice by triggering aberrant microglial activation and BBB disruption through the CRYAB/STAT4-SHH axis, highlighting the potential therapeutic effects of SDMA for the treatment of NPSLE.
{"title":"WIF-1 contributes to lupus-induced neuropsychological deficits via the CRYAB/STAT4-SHH axis","authors":"Liping Tan, Yu Fan, Xinyi Xu, Tianshu Zhang, Xiangyu Cao, Chenghao Zhang, Jun Liang, Yayi Hou, Huan Dou","doi":"10.1186/s13075-024-03420-8","DOIUrl":"https://doi.org/10.1186/s13075-024-03420-8","url":null,"abstract":"Neuropsychiatric systemic lupus erythematosus (NPSLE) often manifests as cognitive deterioration, with activated microglia and blood-brain barrier (BBB) disruption implicated in these neurological complications. Wnt-inhibitory factor-1 (WIF-1), a secreted protein, has been detected in the cerebrospinal fluid (CSF) of NPSLE patients. However, the contribution of WIF-1 in contributing to lupus cognitive impairment remains poorly understood. Using MRL/MpJ-Faslpr (MRL/lpr) lupus-prone mice and TLR7 agonist imiquimod (IMQ)-induced lupus mice, recombinant WIF-1 protein (rWIF-1) and adeno-associated virus (AAV) encoding sh-WIF-1 were administered via intracerebroventricular injection. Behavioral tests, histopathological examinations, flow cytometry, and molecular biology techniques were employed to investigate the underlying mechanisms. Microinjection of rWIF-1 exacerbated cognitive deficits and mood abnormalities, increased BBB leakage and neuronal degeneration, and caused aberrant activation of microglia and synaptic pruning in the hippocampus. Conversely, lupus mice injected with AAV-shWIF-1 exhibited significant remission. In vitro, rWIF-1 induced overactivation of microglia with an increased CD86+ pro-inflammatory subpopulation, upregulated phagocytic activity, and excessive synaptic engulfment, contributing to increased BBB permeability. Furthermore, WIF-1 exerted its biological effects through the CRYAB/STAT4 pathway, transcriptionally decreasing SHH production. We also identified that symmetric dimethylarginine (SDMA) could alleviate rWIF-1-induced microglial activation and BBB damage, thereby restoring SHH levels. In conclusion, WIF-1 exacerbates lupus-induced cognitive dysfunction in mice by triggering aberrant microglial activation and BBB disruption through the CRYAB/STAT4-SHH axis, highlighting the potential therapeutic effects of SDMA for the treatment of NPSLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"60 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1186/s13075-024-03414-6
Xiaoyun Chen, Lianlian Ouyang, Sujie Jia, Ming Zhao
Abnormal oxysterol metabolism has been observed in the peripheral blood of SLE patients, but its role in systemic lupus erythematosus (SLE) skin lesions remains unclear. Targeted oxidized lipid metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS) was performed to quantify oxysterols in SLE skin lesions. Immunohistochemical staining and single-cell sequencing data analysis confirmed the upregulation of oxysterol-encoding enzymes CH25H and CYP7B1. The impact on fibroblast-mediated PBMCs chemotaxis was assessed using a transwell chamber. We identified aberrant oxidized cholesterol metabolism in SLE skin lesions, characterized by elevated levels of 7-ketocholesterol, 5α-6α-cholestane-3β,5α,6β-triol, and so on. Fibroblasts were the primary cells expressing oxysterol-encoding genes, with CH25H and CYP7B1 expression upregulated via the IL-1β-mediated p38 MAPK and NFκB pathways. Notably, IL-1β-stimulated fibroblasts demonstrated enhanced PBMCs recruitment, which was attenuated by a GPR183 inhibitor. Our findings reveal a potential mechanism by which fibroblasts contribute to immune cell recruitment in SLE skin lesions by expression of CH25H and CYP7B1. This study underscores the significance of oxysterol metabolism in SLE skin lesion pathogenesis and highlights potential therapeutic targets for SLE skin lesion treatment. • SLE skin lesions show abnormal oxysterol metabolism, with fibroblasts being the main source of increased CH25H and CYP7B1 genes. • IL-1β-mediated p38 MAPK and NFκB pathways implicated in CH25H and CYP7B1 upregulation. • Enhanced PBMCs recruitment by IL-1β-stimulated fibroblasts can be attenuated by a GPR183 inhibitor, offering potential SLE skin lesion treatment.
{"title":"Oxysterols contribute to immune cell recruitment in SLE skin lesions","authors":"Xiaoyun Chen, Lianlian Ouyang, Sujie Jia, Ming Zhao","doi":"10.1186/s13075-024-03414-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03414-6","url":null,"abstract":"Abnormal oxysterol metabolism has been observed in the peripheral blood of SLE patients, but its role in systemic lupus erythematosus (SLE) skin lesions remains unclear. Targeted oxidized lipid metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS) was performed to quantify oxysterols in SLE skin lesions. Immunohistochemical staining and single-cell sequencing data analysis confirmed the upregulation of oxysterol-encoding enzymes CH25H and CYP7B1. The impact on fibroblast-mediated PBMCs chemotaxis was assessed using a transwell chamber. We identified aberrant oxidized cholesterol metabolism in SLE skin lesions, characterized by elevated levels of 7-ketocholesterol, 5α-6α-cholestane-3β,5α,6β-triol, and so on. Fibroblasts were the primary cells expressing oxysterol-encoding genes, with CH25H and CYP7B1 expression upregulated via the IL-1β-mediated p38 MAPK and NFκB pathways. Notably, IL-1β-stimulated fibroblasts demonstrated enhanced PBMCs recruitment, which was attenuated by a GPR183 inhibitor. Our findings reveal a potential mechanism by which fibroblasts contribute to immune cell recruitment in SLE skin lesions by expression of CH25H and CYP7B1. This study underscores the significance of oxysterol metabolism in SLE skin lesion pathogenesis and highlights potential therapeutic targets for SLE skin lesion treatment. • SLE skin lesions show abnormal oxysterol metabolism, with fibroblasts being the main source of increased CH25H and CYP7B1 genes. • IL-1β-mediated p38 MAPK and NFκB pathways implicated in CH25H and CYP7B1 upregulation. • Enhanced PBMCs recruitment by IL-1β-stimulated fibroblasts can be attenuated by a GPR183 inhibitor, offering potential SLE skin lesion treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"44 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1186/s13075-024-03388-5
Ruiling Feng, Xian Xiao, Bo Huang, Kai Zhang, Xia Zhang, Zhanguo Li, Yuan Jia, Jing He
Low-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE. We pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results. Rash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2. These findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.
{"title":"Predictive biomarkers for low-dose IL-2 therapy efficacy in systemic lupus erythematosus: a clinical analysis","authors":"Ruiling Feng, Xian Xiao, Bo Huang, Kai Zhang, Xia Zhang, Zhanguo Li, Yuan Jia, Jing He","doi":"10.1186/s13075-024-03388-5","DOIUrl":"https://doi.org/10.1186/s13075-024-03388-5","url":null,"abstract":"Low-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE. We pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results. Rash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2. These findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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