Autoimmunity reviews最新文献

{"title":"Dysregulated circular RNAs in rheumatoid arthritis: Cellular roles and clinical prospects","authors":"Mengshi Tang ,&nbsp;Hongxing Li ,&nbsp;Siyuan Chang ,&nbsp;Yuanyuan Li ,&nbsp;Huiyu Nie ,&nbsp;Fen Li","doi":"10.1016/j.autrev.2025.103774","DOIUrl":"10.1016/j.autrev.2025.103774","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is still a healthcare challenge, although current therapeutic strategies have substantially improved its clinical outcomes. The development of novel biomarkers and treatments can increase the likelihood of identification and disease remission in RA patients, especially for patients with seronegative RA and difficult-to-treat RA (D2T RA). Circular RNAs (circRNAs), a novel non-coding RNA species, have been reported to play crucial roles in various biological process of RA. The mechanistic functions of the dysregulated circRNAs in RA are primarily associated with miRNA sponging and regulating transcription. CircRNAs acting as miRNA sponges are further summarized by cell types, including fibroblast-like synoviocytes (FLSs), lymphocytes, macrophages, chondrocytes, and mesenchymal stem cells (MSCs)−/plasma−secreted exosomes. Besides, a description of dysregulated circRNAs in blood, synovial tissue and cartilage tissue suggests their diagnostic potential for RA. In addition, some directions for future research are provided to open the possibility that dysregulated cell- and tissue- specific circRNAs constituting a fresh reservoir of therapeutic targets, and biomarkers for diagnosis, predicting response to therapy, drug selection or patient stratification for RA.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 5","pages":"Article 103774"},"PeriodicalIF":9.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432276","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":"Mucosal immunity and rheumatoid arthritis: An update on mechanisms and therapeutic potential","authors":"Yuchen Yang ,&nbsp;Congmin Xia ,&nbsp;Chuanhui Yao ,&nbsp;Xieli Ma ,&nbsp;Zhengyao Shen ,&nbsp;Peng Chen ,&nbsp;Quan Jiang ,&nbsp;Xun Gong","doi":"10.1016/j.autrev.2025.103775","DOIUrl":"10.1016/j.autrev.2025.103775","url":null,"abstract":"<div><div>Rheumatoid Arthritis (RA) is a persistent autoimmune inflammatory disorder that arises from the intricate interaction between genetic predisposition and environmental influences. The progression of RA can be delineated into four distinct phases: initially, the influence of genetic and environmental risk factors; followed by the emergence of systemic autoimmunity; subsequently, an asymptomatic inflammatory phase; and ultimately, the manifestation of clinical arthritis. Recently, the role of mucosal immunity in RA has gained significant attention in research. Evidence from published studies suggests that mucosal immunity not only influences the onset of RA but also plays a crucial role in its progression. Scholars have begun to unravel the intricate links between RA and the mucosal barriers of the gastrointestinal tract, respiratory system, and oral cavity. Specifically, shifts in the mucosal microbiota, dysfunction of mucosal barriers, and the abnormal activation of mucosal immune tissues are all implicated in the pathogenesis of RA.Despite this growing body of knowledge, a comprehensive review of the abnormal mucosal immunity in RA and its therapeutic implications is yet to be conducted. This review emphasizes the driving role of mucosal immune abnormalities in the development of systemic autoimmunity in rheumatoid arthritis (RA). It further explores the therapeutic potential of mucosal immunity in RA, as well as the issues and challenges that need to be addressed in the current research field, providing a new perspective and potential therapeutic targets for the prevention and treatment of RA.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 5","pages":"Article 103775"},"PeriodicalIF":9.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424917","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":"Oligoclonal bands and kappa free light chains: Competing parameters or complementary biomarkers?","authors":"Franz F. Konen ,&nbsp;Ulrich Wurster ,&nbsp;Philipp Schwenkenbecher ,&nbsp;Andreas Gerritzen ,&nbsp;Catharina C. Groß ,&nbsp;Peter Eichhorn ,&nbsp;Andrea Harrer ,&nbsp;Stefan Isenmann ,&nbsp;Piotr Lewczuk ,&nbsp;Jan Lewerenz ,&nbsp;Frank Leypoldt ,&nbsp;Markus Otto ,&nbsp;Axel Regeniter ,&nbsp;Martin Roskos ,&nbsp;Klemens Ruprecht ,&nbsp;Annette Spreer ,&nbsp;Herwig Strik ,&nbsp;Manfred Uhr ,&nbsp;Manfred Wick ,&nbsp;Brigitte Wildemann ,&nbsp;Thomas Skripuletz","doi":"10.1016/j.autrev.2025.103765","DOIUrl":"10.1016/j.autrev.2025.103765","url":null,"abstract":"<div><h3>Background</h3><div>The 2024-revised McDonald criteria for multiple sclerosis (MS) proposed to incorporate cerebrospinal fluid (CSF)-specific oligoclonal bands and kappa free light chains (KFLC) as diagnostic biomarkers. While the 2017-revised criteria highlighted CSF-specific oligoclonal bands to indicate intrathecal IgG synthesis, significantly enhancing early MS diagnosis, KFLC have emerged as additional marker. Now, the question rises of whether both biomarkers serve as competing or complementary tools in MS diagnostics.</div></div><div><h3>Methods</h3><div>In this narrative review, we extensively searched the literature on oligoclonal bands and KFLC determination in CSF and serum across neurological disorders, with a focus on MS, using the PubMed database to demonstrate the complementarity of both biomarkers.</div></div><div><h3>Results</h3><div>Oligoclonal bands have long been a reliable marker of intrathecal IgG synthesis in MS, valued for their high diagnostic sensitivity, unique patient “fingerprints,” clonality differentiation, semi-quantitative analysis, and pre-analytic robustness. However, they present challenges in standardization, labor-intensity, method variability, examiner dependency, and limited data on non-IgG immunoglobulins. Quantitative KFLC measurement provides rapid, examiner-independent, and cost-effective assessment across all immunoglobulin classes but might have lower specificity, lacked consensus on standardized interpretation in recent years, and is not yet supported by comprehensive prospective multinational studies on its prognostic role.</div></div><div><h3>Conclusion</h3><div>Both oligoclonal bands and KFLC have unique strengths and limitations that complement each other, potentially serving as complementary markers for evaluating intrathecal Ig synthesis in MS diagnosis. Further evidence is needed to establish the value of KFLC in MS diagnosis, thus multicenter prospective studies are being conducted to compare the diagnostic utility of both markers.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 5","pages":"Article 103765"},"PeriodicalIF":9.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413294","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":"ABCE1: A new cytoplasmic autoantibody target in systemic sclerosis-associated interstitial lung disease","authors":"Jean-Baptiste Vulsteke ,&nbsp;Jan Lenaerts ,&nbsp;Doreen Dillaerts ,&nbsp;Patrick Verschueren ,&nbsp;Wim A. Wuyts ,&nbsp;Nico De Crem ,&nbsp;Laurens De Sadeleer ,&nbsp;Robin Vos ,&nbsp;Ellen De Langhe ,&nbsp;Xavier Bossuyt","doi":"10.1016/j.autrev.2025.103764","DOIUrl":"10.1016/j.autrev.2025.103764","url":null,"abstract":"","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 5","pages":"Article 103764"},"PeriodicalIF":9.2,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388004","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":"The role of social determinants of health on disease outcomes in axial spondyloarthritis: A narrative review","authors":"Dafne Capelusnik ,&nbsp;Annelies Boonen ,&nbsp;Sofia Ramiro ,&nbsp;Elena Nikiphorou","doi":"10.1016/j.autrev.2025.103762","DOIUrl":"10.1016/j.autrev.2025.103762","url":null,"abstract":"<div><div>This review provides a narrative exploration of the literature on various social determinants of health that influence outcomes in axial Spondyloarthritis (axSpA). By using the PROGRESS-Plus framework (place of residence, race, occupation, gender/sex, religion, education, socioeconomic status, social capital, age), this review discusses how these factors have been studied and their impact on disease outcomes in axSpA. The findings suggest that various patient-level factors (e.g. female sex, blue-collar jobs, low educational level) and country-level factors (e.g. low-income countries) associate with worse health outcomes in axSpA. These insights highlight the importance of adopting a multifaceted and holistic approach, that also considers social determinants of health, when managing patients with axSpA. This work also identifies unmet needs in this area including the importance of thinking beyond just biological factors, when considering drivers of suboptimal outcomes in axSpA.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 5","pages":"Article 103762"},"PeriodicalIF":9.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373527","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":"Complement-coagulation crosstalk in idiopathic membranous nephropathy: The potential pathogenesis and therapeutic perspective","authors":"Zikang Liu ,&nbsp;Wei Liang ,&nbsp;Yangbin Pan","doi":"10.1016/j.autrev.2025.103763","DOIUrl":"10.1016/j.autrev.2025.103763","url":null,"abstract":"<div><div>Idiopathic membranous nephropathy (IMN) is a glomerular disease that is prevalent in elderly males. The pathogenesis of IMN includes abnormal autoimmunity and complement activation, both of which leading to the damage of the glomerular filtration structure. Meanwhile, due to the pathological changes in the kidney, certain coagulation-related proteins are leaked from urine, resulting in the imbalance of coagulation homeostasis. Recent studies have indicated the interaction between complement and coagulation systems, while the aberration of both is common in IMN. In this review, we summarize the subsistent and underlying pathogenesis that ensue from complement-coagulation crosstalk and present the emerging evidence in this evolving field.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 5","pages":"Article 103763"},"PeriodicalIF":9.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363445","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":"Immunomodulation for accelerated atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus","authors":"Elena Bartoloni ,&nbsp;Fabio Cacciapaglia ,&nbsp;Gian Luca Erre ,&nbsp;Elisa Gremese ,&nbsp;Andreina Manfredi ,&nbsp;Matteo Piga ,&nbsp;Garifallia Sakellariou ,&nbsp;Francesca Romana Spinelli ,&nbsp;Ombretta Viapiana ,&nbsp;Fabiola Atzeni","doi":"10.1016/j.autrev.2025.103760","DOIUrl":"10.1016/j.autrev.2025.103760","url":null,"abstract":"<div><div>In the last decades, consisting evidence supported a close relationship between both innate and adaptive immune systems and the accelerated cardiovascular (CV) disease characterizing autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Indeed, several cell lines involved in the pathogenesis of these autoimmune diseases, such as macrophages and dendritic cells, as well as different T and B lymphocyte subsets, and inflammatory cytokines, have been demonstrated to be directly involved in the mechanisms underlying early atherosclerotic arterial wall damage. Traditional CV risk factors play a concomitant role but do not sufficiently account for the increased prevalence of CV disease in these patients. Indeed, the pathophysiological link between RA and SLE and atherosclerosis is based on complex inflammatory pathways that interconnect these conditions and may explain the significant morbidity and mortality rates demonstrated in these patients, with consequent significant negative effects on quality of life and long-term survival. Consequently, it is intriguing to hypothesize that immunosuppressive drugs commonly used in the treatment of these pathologies may also exert an immunomodulatory and anti-inflammatory effect in mitigating the atherosclerotic damage that has been demonstrated to occur early in the initial stages of the disease. Recognizing risk factors, predicting occurrences and early intervention to prevent CV disease development have emerged as critical objectives in RA and SLE treatment. In this review, we aimed to provide an updated overview of the atherogenic effects exerted by the immune and inflammatory pathways involved in the pathogenesis of RA and SLE. Moreover, we examined the available evidence which may support the potential effects of immunosuppressive therapies in reducing CV damage and, consequently, CV disease risk in these patients.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 4","pages":"Article 103760"},"PeriodicalIF":9.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078513","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":"Characteristics and risk factors for infection in patients with ANCA-associated vasculitis: A systematic review and meta-analysis","authors":"Wenxuan Luo ,&nbsp;Can Liu ,&nbsp;Lei Zhang ,&nbsp;Jie Tang ,&nbsp;Jie Chen ,&nbsp;Yanzao Zhao ,&nbsp;Xuemei Huang ,&nbsp;Xiaoli Zheng ,&nbsp;Long Chen ,&nbsp;Chuanmei Xie ,&nbsp;Xin Wei ,&nbsp;Xiongyan Luo ,&nbsp;Anji Xiong","doi":"10.1016/j.autrev.2024.103713","DOIUrl":"10.1016/j.autrev.2024.103713","url":null,"abstract":"<div><h3>Objective</h3><div>To summarize the characteristics and risk factors for infection in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).</div></div><div><h3>Methods</h3><div>PubMed, Embase, and Cochrane Library databases were searched for relevant articles from database inception to November 2023. The prevalence, odds ratio (OR), and mean difference (MD) with 95 % confidence intervals (CIs) were pooled using a random-effects model. Sensitivity and subgroup analysis were also performed.</div></div><div><h3>Results</h3><div>Forty-one studies with 5343 patients with AAV were included, of whom 2890 patients experienced an infection. The pooled prevalence was 54.6 % (95 % CI, 48.4 % to 61.1 %) for all infections and 35.8 % (95 % CI, 31.0 % to 40.8 %) for severe infections; and prevalence of <em>Pneumocystis jirovecii</em> pneumonia, aspergillosis, candidiasis, cryptococcosis, herpes zoster, cytomegalovirus, and specific bacterial infections were pooled. The respiratory system was the most common infection site, followed by blood, urinary tract, skin and soft tissue, and digestive infections. Risk factors for infection included older age, end-stage renal disease, dialysis, diabetes, smoking, kidney and lung involvement, leukopenia; higher Birmingham Vasculitis Activity Score, and serum creatinine and C-reactive protein levels; and lower hemoglobin levels, and platelet and CD4 counts. In addition, use of cyclophosphamide, steroid pulse therapy, plasma exchange, and higher initial glucocorticoid dose were associated with significantly increased risk of infection.</div></div><div><h3>Conclusion</h3><div>In patients with AAV, therapy should take risk factors for infection into account. Risk factors should be modified wherever possible. Physicians should be familiar with the common infection sites and pathogens, and consider empiric therapy covering common pathogens for life-threatening infections.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 2","pages":"Article 103713"},"PeriodicalIF":9.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765914","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":"Differences in clinical phenotype, laboratory, and imaging manifestations between AQP4 IgG positive and AQP4 MOG IgG double negative NMOSD: How to correctly diagnose the two","authors":"Fengna Chu ,&nbsp;Mingchao Shi ,&nbsp;Jie Zhu","doi":"10.1016/j.autrev.2025.103761","DOIUrl":"10.1016/j.autrev.2025.103761","url":null,"abstract":"<div><div>Neuromyelitis optica spectrum disorders (NMOSD) is an uncommon autoimmune inflammatory demyelinating disorder of the central nervous system (CNS) and causes severe disability and even death. Aquaporin-4 immunoglobulin G (AQP4-IgG) antibody has been confirmed as the key pathogenic factor for development of NMOSD and leading to repeatting acute attacks. However, 20–40 % of NMOSD patients lack both AQP4-IgG and anti-myelin oligodendrocytes glycoproteins (MOG) IgG, in which the pathogenic factor is still unclear. There are differences in clinical, laboretory and imaiging minifestations between AQP4-IgG positive (AQP4-IgG⁺) and AQP4-IgG/MOG-IgG double negative (AQP4-IgG⁻) NMOSD. Although the treatments applied in NMOSD have made great progress, all treatments are failed in AQP4-IgG⁻ patients. Additionally, it is hard to identify NMOSD with AQP4-IgG⁻ from multiple sclerosis (MS). Therefore, it is suspected and challenged that AQP4-IgG could not be the only pathogenic factor in NMOSD or NMOSD with AQP4-IgG⁻ may be a separate disorder independent of NMOSD AQP4-IgG⁺? It is necessary to find more pathogenic factors and to explore the new pathogenesis and treatments of NMOSD with AQP4-IgG⁻ in the future, which has been a serious problem to be addressed by the neurology community.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 4","pages":"Article 103761"},"PeriodicalIF":9.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073564","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":"Current landscape of monogenic autoinflammatory actinopathies: A literature review","authors":"P. Mertz ,&nbsp;V. Hentgen ,&nbsp;G. Boursier ,&nbsp;J. Delon ,&nbsp;S. Georgin-Lavialle","doi":"10.1016/j.autrev.2024.103715","DOIUrl":"10.1016/j.autrev.2024.103715","url":null,"abstract":"<div><div>Autoinflammatory diseases (AID) are conditions leading to a hyperactivation of innate immunity without any underlying infection, and may be poly- (e.g. Still's disease) or monogenic. The number of monogenic AID is continuously expanding, with the discovery of novel pathologies and pathophysiological mechanisms, facilitated in part by easier access to pangenomic sequencing. Actinopathies with autoinflammatory manifestations represent a newly emerging subgroup of AID, associated with defects in the regulation of actin cytoskeleton dynamics. These diseases typically manifest in the neonatal period and variably combine a primary immunodeficiency of varying severity, cytopenia (particularly thrombocytopenia), autoinflammatory manifestations primarily affecting the skin and digestive system, as well as atopic and autoimmune features.</div><div>Diagnosis should be considered primarily when encountering an early-onset autoinflammatory skin and digestive disorder, along with a primary immunodeficiency and either thrombocytopenia or a bleeding tendency. Some of these diseases exhibit specific features, such as a risk of macrophage activation syndrome (MAS) or a predisposition to atopy or lymphoproliferation. The complete pathophysiology of these diseases is not yet fully understood, and further studies are required to elucidate the underlying mechanisms, which could guide therapeutic choices. In most cases, the severity of the conditions necessitates allogeneic marrow transplantation as a treatment option.</div><div>In this review, we discuss these novel diseases, providing a practical approach based on the main associated biological abnormalities and specific clinical characteristics, with a special focus on the newly described actinopathies <em>DOCK11</em> and <em>ARPC5</em> deficiency. Nonetheless, genetic testing remains essential for definitive diagnosis, and various differential diagnoses must be considered.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"24 2","pages":"Article 103715"},"PeriodicalIF":9.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791024","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}