Pub Date : 2024-11-14DOI: 10.1016/j.jtauto.2024.100261
Ning Cao , Wenxi Dang , Yanguo Xin , Jiayu Li , Shaohua Guo , Qitian Li , Hui Chen , Shun Li
Backgrounds
Coronary microvascular obstruction (MVO) frequently occurs in patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI), leading to poor prognosis. β1 adrenergic receptor autoantibodies (β1-AA) are present in various cardiovascular diseases and correlate with cardiac damage and dysfunction. However, whether β1-AA is associated with the occurrence of MVO in patients with STEMI after PCI remains unclear.
Aims
To investigate the prognostic relationship between β1-AA and the occurrence of MVO in patients with STEMI with post-PCI.
Methods
This prospective study included 403 patients with STEMI who underwent primary PCI. The patients were divided into MVO+ and MVO- groups. Serum β1-AA levels were measured prior to primary PCI. The primary outcome was MVO, assessed through cardiac magnetic resonance imaging at 5–7 days after PCI.
Results
A total of 127 MVO+ and 276 MVO– patients were identified. Patients with MVO + exhibited higher β1-AA optical density (OD) compared to MVO- patients. β1-AA OD, pNT-proBNP, pCK-MB and pTNI were positively associated with MVO following PCI. Notably, the assocition between β1-AA levels and MVO risk strengthened with increasing pNT-proBNP levels. The combination of β1-AA, pNT-proBNP and pTNI yielded the most efficient MVO prediction with an area under the ROC curve of 0.87 (95 % CI: 0.83–0.90).
Conclusions
β1-AA is significantly associated with the occurrence of MVO in STEMI patients following primary PCI. The combination of β1-AA with pNT-proBNP and pTNI improves predictive accuracy, providing a more robust and effective strategy for assessing MVO risk.
{"title":"Prognostic value of β1 adrenergic receptor autoantibodies for microvascular obstruction in patients with STEMI with Post-PCI: A prospective cohort study","authors":"Ning Cao , Wenxi Dang , Yanguo Xin , Jiayu Li , Shaohua Guo , Qitian Li , Hui Chen , Shun Li","doi":"10.1016/j.jtauto.2024.100261","DOIUrl":"10.1016/j.jtauto.2024.100261","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Coronary microvascular obstruction (MVO) frequently occurs in patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI), leading to poor prognosis. β<sub>1</sub> adrenergic receptor autoantibodies (β<sub>1</sub>-AA) are present in various cardiovascular diseases and correlate with cardiac damage and dysfunction. However, whether β<sub>1</sub>-AA is associated with the occurrence of MVO in patients with STEMI after PCI remains unclear.</div></div><div><h3>Aims</h3><div>To investigate the prognostic relationship between β<sub>1</sub>-AA and the occurrence of MVO in patients with STEMI with post-PCI.</div></div><div><h3>Methods</h3><div>This prospective study included 403 patients with STEMI who underwent primary PCI. The patients were divided into MVO+ and MVO- groups. Serum β<sub>1</sub>-AA levels were measured prior to primary PCI. The primary outcome was MVO, assessed through cardiac magnetic resonance imaging at 5–7 days after PCI.</div></div><div><h3>Results</h3><div>A total of 127 MVO+ and 276 MVO– patients were identified. Patients with MVO + exhibited higher β<sub>1</sub>-AA optical density (OD) compared to MVO- patients. β<sub>1</sub>-AA OD, pNT-proBNP, pCK-MB and pTNI were positively associated with MVO following PCI. Notably, the assocition between β<sub>1</sub>-AA levels and MVO risk strengthened with increasing pNT-proBNP levels. The combination of β<sub>1</sub>-AA, pNT-proBNP and pTNI yielded the most efficient MVO prediction with an area under the ROC curve of 0.87 (95 % CI: 0.83–0.90).</div></div><div><h3>Conclusions</h3><div>β<sub>1</sub>-AA is significantly associated with the occurrence of MVO in STEMI patients following primary PCI. The combination of β<sub>1</sub>-AA with pNT-proBNP and pTNI improves predictive accuracy, providing a more robust and effective strategy for assessing MVO risk.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100261"},"PeriodicalIF":4.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142661280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.jtauto.2024.100257
Elizabeth M. Ortega Rocha , Paul Hernández-Herrera , Sofia V. de los Santos- Carmona , Saraí G De León-Rodríguez , Ángel Juárez-Flores , Vadim Pérez-Koldenkova , Octavio Castro-Escamilla , Samira Muñoz-Cruz , Alicia Lemini-López , Laura C. Bonifaz
Psoriasis is a chronic inflammatory autoimmune skin disease characterized by keratinocyte hyperproliferation, primarily driven by the IL-23/IL-17 axis. In addition to immune response, various skin components, including the epidermal barrier and the skin microbiota, have been individually implicated in the disease pathogenesis. Here, we aimed to investigate the interplay between epidermal tight junctions, Staphylococcus aureus enterotoxin B (SEB), and CD4 T cell-mediated immune responses. By immunofluorescence analyses of skin biopsies, we observed that claudin-1 distribution was significantly altered in psoriatic patients, which correlated with the localization of Staphylococcus aureus and SEB across skin layers and with disease severity. Furthermore, functional CD4 TCRvβ17 cells were associated with SEB presence in patients skin and positively correlated with psoriasis severity. Notably, in patients with SEB detected in the dermis, CD4 TCRvβ17 IL-17 cells were linked to barrier abnormalities.
Unsupervised analysis stratified psoriasis patients into three groups based on SEB presence and location, supporting the previous findings. The patient group with SEB in the dermis exhibited improved responses to biological therapy, including reductions in PASI score, claudin-1 fragmentation, S. aureus and SEB presence, and CD4 TCRvβ17 cell percentages. Our findings emphasize the complex interplay between epidermal barrier distribution, SEB localization, and functional CD4 TCRvβ17 cells in psoriatic skin, highlighting their potential in patient stratification in association with the severity of the disease.
{"title":"The interplay between epidermal barrier distribution, microbiota composition, and immune infiltrate defines and stratifies psoriasis patients and is associated with disease severity","authors":"Elizabeth M. Ortega Rocha , Paul Hernández-Herrera , Sofia V. de los Santos- Carmona , Saraí G De León-Rodríguez , Ángel Juárez-Flores , Vadim Pérez-Koldenkova , Octavio Castro-Escamilla , Samira Muñoz-Cruz , Alicia Lemini-López , Laura C. Bonifaz","doi":"10.1016/j.jtauto.2024.100257","DOIUrl":"10.1016/j.jtauto.2024.100257","url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory autoimmune skin disease characterized by keratinocyte hyperproliferation, primarily driven by the IL-23/IL-17 axis. In addition to immune response, various skin components, including the epidermal barrier and the skin microbiota, have been individually implicated in the disease pathogenesis. Here, we aimed to investigate the interplay between epidermal tight junctions, Staphylococcus aureus enterotoxin B (SEB), and CD4 T cell-mediated immune responses. By immunofluorescence analyses of skin biopsies, we observed that claudin-1 distribution was significantly altered in psoriatic patients, which correlated with the localization of <em>Staphylococcus aureus</em> and SEB across skin layers and with disease severity. Furthermore, functional CD4 TCRvβ17 cells were associated with SEB presence in patients skin and positively correlated with psoriasis severity. Notably, in patients with SEB detected in the dermis, CD4 TCRvβ17 IL-17 cells were linked to barrier abnormalities.</div><div>Unsupervised analysis stratified psoriasis patients into three groups based on SEB presence and location, supporting the previous findings. The patient group with SEB in the dermis exhibited improved responses to biological therapy, including reductions in PASI score, claudin-1 fragmentation, <em>S. aureus</em> and SEB presence, and CD4 TCRvβ17 cell percentages. Our findings emphasize the complex interplay between epidermal barrier distribution, SEB localization, and functional CD4 TCRvβ17 cells in psoriatic skin, highlighting their potential in patient stratification in association with the severity of the disease.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100257"},"PeriodicalIF":4.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142661141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.jtauto.2024.100259
Yulin Bao , Lingfeng Gu , Jiayi Chen , Hao Wang , Zemu Wang , Huijuan Wang , Sibo Wang , Liansheng Wang
Backgroud
Autoimmune diseases (AIDs) have been associated with various cardiovascular diseases (CVDs) in observational data. However, the causality of these associations remains uncertain. Therefore, a systematic assessment of the impact of AIDS on cardiovascular risk is required.
Results
We assessed the impact of 19 common AIDs on 14 CVDs using bidirectional Mendelian randomization (MR). Celiac disease (odds ratio [OR] = 2.949, 95 % confidence interval [CI]: 1.111–7.827, P = 0.030) and type 1 diabetes mellitus (T1DM) (OR = 1.044, 95 % CI: 1.021–1.068, P = 1.82e-4) were associated with an increased risk of peripheral arterial disease (PAD). Additionally, celiac disease was linked to an increased risk of arrhythmia (OR = 1.008, 95 % CI: 1.002–1.013, P = 0.004), multiple sclerosis to venous thromboembolism (OR = 1.001, 95 % CI: 1.000–1.001, P = 0.010), and psoriasis to heart failure (OR = 1.048, 95 % CI: 1.021–1.077, P = 0.001). Sensitivity analyses were conducted to enhance the robustness of these findings. Predominantly, immune response and inflammation-related pathways were enriched in the aforementioned associations. Mediation analysis identified human leukocyte antigen-DR positive myeloid dendritic cells as partially mediating the effect of T1DM on PAD, with a mediated proportion of 16.61 % (P = 0.028). Potential therapeutic agents, such as tumor necrosis factor-alpha inhibitors and interferon, may have efficacy in treating AID-related CVDs.
Conclusions
This study presents genetic evidence of certain AIDs impacting specific CVDs and identifies potential mediators and drugs.
{"title":"Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions","authors":"Yulin Bao , Lingfeng Gu , Jiayi Chen , Hao Wang , Zemu Wang , Huijuan Wang , Sibo Wang , Liansheng Wang","doi":"10.1016/j.jtauto.2024.100259","DOIUrl":"10.1016/j.jtauto.2024.100259","url":null,"abstract":"<div><h3>Backgroud</h3><div>Autoimmune diseases (AIDs) have been associated with various cardiovascular diseases (CVDs) in observational data. However, the causality of these associations remains uncertain. Therefore, a systematic assessment of the impact of AIDS on cardiovascular risk is required.</div></div><div><h3>Results</h3><div>We assessed the impact of 19 common AIDs on 14 CVDs using bidirectional Mendelian randomization (MR). Celiac disease (odds ratio [OR] = 2.949, 95 % confidence interval [CI]: 1.111–7.827, P = 0.030) and type 1 diabetes mellitus (T1DM) (OR = 1.044, 95 % CI: 1.021–1.068, P = 1.82e-4) were associated with an increased risk of peripheral arterial disease (PAD). Additionally, celiac disease was linked to an increased risk of arrhythmia (OR = 1.008, 95 % CI: 1.002–1.013, P = 0.004), multiple sclerosis to venous thromboembolism (OR = 1.001, 95 % CI: 1.000–1.001, P = 0.010), and psoriasis to heart failure (OR = 1.048, 95 % CI: 1.021–1.077, P = 0.001). Sensitivity analyses were conducted to enhance the robustness of these findings. Predominantly, immune response and inflammation-related pathways were enriched in the aforementioned associations. Mediation analysis identified human leukocyte antigen-DR positive myeloid dendritic cells as partially mediating the effect of T1DM on PAD, with a mediated proportion of 16.61 % (P = 0.028). Potential therapeutic agents, such as tumor necrosis factor-alpha inhibitors and interferon, may have efficacy in treating AID-related CVDs.</div></div><div><h3>Conclusions</h3><div>This study presents genetic evidence of certain AIDs impacting specific CVDs and identifies potential mediators and drugs.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100259"},"PeriodicalIF":4.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dysregulated T cell homeostasis has long been implicated in the pathogenesis of rheumatoid arthritis (RA), in the joint of which peripheral helper T (Tph) cells accumulate and form ectopic lymphoid organs. We examined whether homeostatic signals are involved in the development of Tph cells.
Methods
Human peripheral blood mononuclear cells were cultured with IL-7, the critical cytokine for T cell homeostasis. Development of Tph-like cells was assessed by flow cytometry, gene expression, and functional analysis. Chemotaxis of the Tph-like cells to RA synovial fluid (RASF) and the effect of RASF on the development of Tph-like cells was examined.
Results
PD-1highCXCR5- Tph-like cells developed from human peripheral blood CD4 T cells after proliferation in response to IL-7. Signals from self-MHC recognition and CD28 co-stimulation were also involved. The IL-7-induced Tph-like (IL-7-Tph) cells produced CXCL13 and IL-21 and helped B cells produce IgG. Comprehensive gene expression analysis further supported the similarity with Tph cells in RA joint. IL-7-Tph cells exhibited chemotaxis toward synovial fluid from RA patients (RASF), and RASF promoted the development of IL-7-Tph cells, which were also induced from CD4 T cells residing in non-inflamed joints.
Conclusions
Our results demonstrate an antigen-nonspecific developmental pathway of Tph cells triggered by homeostatic signals and promoted by the local environment of RA, which accounts for the accumulation of Tph cells in inflamed joints.
目的长期以来，T细胞稳态失调一直被认为与类风湿性关节炎（RA）的发病机制有关，在类风湿性关节炎的关节中，外周辅助性T细胞（Tph）聚集并形成异位淋巴器官。我们研究了平衡信号是否参与了 Tph 细胞的发育。方法用 IL-7 培养人外周血单核细胞，IL-7 是 T 细胞平衡的关键细胞因子。通过流式细胞术、基因表达和功能分析评估了Tph样细胞的发育情况。研究了Tph样细胞对RA滑液（RASF）的趋化作用以及RASF对Tph样细胞发育的影响。来自自身-MHC 识别和 CD28 协同刺激的信号也参与其中。IL-7诱导的Tph样细胞（IL-7-Tph）能产生CXCL13和IL-21，并帮助B细胞产生IgG。全面的基因表达分析进一步证实了与 RA 关节中 Tph 细胞的相似性。IL-7-Tph细胞对来自RA患者的滑液（RASF）表现出趋化性，RASF促进了IL-7-Tph细胞的发育，而这些细胞也是从非炎症关节中的CD4 T细胞中诱导出来的。
{"title":"Homeostatic signals, including IL-7 and self-MHC recognition, induce the development of peripheral helper T cells, which are enriched in the joints of rheumatoid arthritis","authors":"Ryosuke Tsurui , Hisakata Yamada , Takahiro Natori , Motoki Yoshimura , Yukio Akasaki , Shinya Kawahara , Hiroaki Niiro , Yuya Kunisaki , Yasuharu Nakashima","doi":"10.1016/j.jtauto.2024.100258","DOIUrl":"10.1016/j.jtauto.2024.100258","url":null,"abstract":"<div><h3>Objective</h3><div>Dysregulated T cell homeostasis has long been implicated in the pathogenesis of rheumatoid arthritis (RA), in the joint of which peripheral helper T (Tph) cells accumulate and form ectopic lymphoid organs. We examined whether homeostatic signals are involved in the development of Tph cells.</div></div><div><h3>Methods</h3><div>Human peripheral blood mononuclear cells were cultured with IL-7, the critical cytokine for T cell homeostasis. Development of Tph-like cells was assessed by flow cytometry, gene expression, and functional analysis. Chemotaxis of the Tph-like cells to RA synovial fluid (RASF) and the effect of RASF on the development of Tph-like cells was examined.</div></div><div><h3>Results</h3><div>PD-1<sup>high</sup>CXCR5<sup>-</sup> Tph-like cells developed from human peripheral blood CD4 T cells after proliferation in response to IL-7. Signals from self-MHC recognition and CD28 co-stimulation were also involved. The IL-7-induced Tph-like (IL-7-Tph) cells produced CXCL13 and IL-21 and helped B cells produce IgG. Comprehensive gene expression analysis further supported the similarity with Tph cells in RA joint. IL-7-Tph cells exhibited chemotaxis toward synovial fluid from RA patients (RASF), and RASF promoted the development of IL-7-Tph cells, which were also induced from CD4 T cells residing in non-inflamed joints.</div></div><div><h3>Conclusions</h3><div>Our results demonstrate an antigen-nonspecific developmental pathway of Tph cells triggered by homeostatic signals and promoted by the local environment of RA, which accounts for the accumulation of Tph cells in inflamed joints.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100258"},"PeriodicalIF":4.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.jtauto.2024.100254
Nelly Candela , Nicolas Benichou , Mathilde Lefebvre , Lorraine Gueguen , Paula Vieira-Martins , Carine El Sissy , Hervé Sartelet , Pascale Testevuide , Ronan Delaval , Stanislas Faguer
Objective
To compare the natural history of C3 glomerulopathy (C3G) to acute post-infectious glomerulonephritis (APIGN) in a cohort of patients with a relative homogeneity of environment conditions and genetic background.
Methods
We retrospectively reviewed the characteristics of all patients with biopsy proven C3G or APIGN referred in 2013–2019 to the only renal unit in French Polynesia.
Results
Point prevalence of C3G is ∼23 cases per 100,000 inhabitants. A recurrent variation of CFI (p.Arg406His) was identified at the heterozygous state in 4/8 (50 %) patients with C3G but its pathogenicity remain elusive. Characteristics at presentation and kidney outcomes were roughly similar between C3G (n = 16) and APIGN (n = 20), excepted for the presence of humps on kidney biopsy.
Conclusions
C3G is highly prevalent in French Polynesia suggesting specific genetic or environmental susceptibility factors. Systematic diagnosis workflow should be proposed to all patients with C3 predominant glomerulonephritis.
{"title":"C3 glomerulopathy is highly prevalent in French Polynesia","authors":"Nelly Candela , Nicolas Benichou , Mathilde Lefebvre , Lorraine Gueguen , Paula Vieira-Martins , Carine El Sissy , Hervé Sartelet , Pascale Testevuide , Ronan Delaval , Stanislas Faguer","doi":"10.1016/j.jtauto.2024.100254","DOIUrl":"10.1016/j.jtauto.2024.100254","url":null,"abstract":"<div><h3>Objective</h3><div>To compare the natural history of C3 glomerulopathy (C3G) to acute post-infectious glomerulonephritis (APIGN) in a cohort of patients with a relative homogeneity of environment conditions and genetic background.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed the characteristics of all patients with biopsy proven C3G or APIGN referred in 2013–2019 to the only renal unit in French Polynesia.</div></div><div><h3>Results</h3><div>Point prevalence of C3G is ∼23 cases per 100,000 inhabitants. A recurrent variation of CFI (p.Arg406His) was identified at the heterozygous state in 4/8 (50 %) patients with C3G but its pathogenicity remain elusive. Characteristics at presentation and kidney outcomes were roughly similar between C3G (n = 16) and APIGN (n = 20), excepted for the presence of humps on kidney biopsy.</div></div><div><h3>Conclusions</h3><div>C3G is highly prevalent in French Polynesia suggesting specific genetic or environmental susceptibility factors. Systematic diagnosis workflow should be proposed to all patients with C3 predominant glomerulonephritis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100254"},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-26DOI: 10.1016/j.jtauto.2024.100256
Yi-Xin Cai , Xiao-Li Chen , Dai-Shan Zheng , Yue-Zhong Huang , Zhan-Pei Bai , Xiu-Feng Huang
Background
Juvenile idiopathic arthritis (JIA) is a prevalent chronic rheumatic disease affecting children. Current medications merely alleviate symptoms rather than curing the disease. Hence, the identification and development of novel drug targets and biomarkers for JIA are imperative for enhancing treatment efficacy.
Methods
We employed two-sample Mendelian randomization (MR) analysis to investigate the causal effects of plasma proteins on JIA. Additionally, colocalization, bulk RNA-seq, and single-cell RNA-seq analyses were conducted to further investigate and validate the potential of candidate proteins as drug targets.
Results
Through MR analysis, we successfully identified five plasma proteins that are causally linked to JIA. Genetically inferred lower levels of AIF1, TNF, and TNFSF11 were associated with an elevated risk of JIA, while higher levels of AGER and GP1BA proteins were positively correlated with JIA risk. Colocalization analysis further supported our findings on GP1BA (OR = 9.26, 95 % CI: 2.30–37.20) and TNFSF11 (OR = 0.18, 95 % CI: 0.07–0.45). Based on this evidence, we classified these five proteins into two tiers. Finally, we conducted a systematic evaluation of the druggability and current drug development progress for these identified candidate proteins.
Conclusions
This study employed MR analysis to reveal causal relationships between plasma proteins and JIA, identifying five potential candidate proteins as promising drug targets for JIA, particularly focusing on GP1BA and TNFSF11.
{"title":"Integrated analysis of multi-omics data for the discovery of biomarkers and therapeutic targets for juvenile idiopathic arthritis","authors":"Yi-Xin Cai , Xiao-Li Chen , Dai-Shan Zheng , Yue-Zhong Huang , Zhan-Pei Bai , Xiu-Feng Huang","doi":"10.1016/j.jtauto.2024.100256","DOIUrl":"10.1016/j.jtauto.2024.100256","url":null,"abstract":"<div><h3>Background</h3><div>Juvenile idiopathic arthritis (JIA) is a prevalent chronic rheumatic disease affecting children. Current medications merely alleviate symptoms rather than curing the disease. Hence, the identification and development of novel drug targets and biomarkers for JIA are imperative for enhancing treatment efficacy.</div></div><div><h3>Methods</h3><div>We employed two-sample Mendelian randomization (MR) analysis to investigate the causal effects of plasma proteins on JIA. Additionally, colocalization, bulk RNA-seq, and single-cell RNA-seq analyses were conducted to further investigate and validate the potential of candidate proteins as drug targets.</div></div><div><h3>Results</h3><div>Through MR analysis, we successfully identified five plasma proteins that are causally linked to JIA. Genetically inferred lower levels of AIF1, TNF, and TNFSF11 were associated with an elevated risk of JIA, while higher levels of AGER and GP1BA proteins were positively correlated with JIA risk. Colocalization analysis further supported our findings on GP1BA (OR = 9.26, 95 % CI: 2.30–37.20) and TNFSF11 (OR = 0.18, 95 % CI: 0.07–0.45). Based on this evidence, we classified these five proteins into two tiers. Finally, we conducted a systematic evaluation of the druggability and current drug development progress for these identified candidate proteins.</div></div><div><h3>Conclusions</h3><div>This study employed MR analysis to reveal causal relationships between plasma proteins and JIA, identifying five potential candidate proteins as promising drug targets for JIA, particularly focusing on GP1BA and TNFSF11.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100256"},"PeriodicalIF":4.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.jtauto.2024.100255
Jia Di , Xiaodong Ma , Tao Wu , Eryue Qiao , Mojtaba Salouti , Yu Zhong , Qian Xia , Danfeng Kong , Min Hao , Qingwei Xie , Zhuang Ge , Dongzheng Liu , Juanyi Feng , Xianghong Zheng
<div><h3>Background</h3><div>Since the end of the COVID-19 pandemic, the potential roles of thyroid-inflammatory derangements in driving or being associated with the prognosis of COVID-19 remain controversial. We aimed to clarify the association between COVID-19 infection and thyroid dysfunction, and highlight the impacts of subsequent autoimmune thyroid disease (AITD) on the prognosis of COVID-19.</div></div><div><h3>Methods</h3><div>The retrospective, multicenter, cohort study enrolled 2,339 participants with COVID-19 from three hospitals located in the north, middle, and south regions of Shaan Xi Province, China, between December 2022 and July 2023. 464 non-COVID-19 patients within the same period were supplemented, divided into groups with and without AITD. At hospital admission (baseline), 3- and 6-month follow-ups, we presented a dynamic description and correlation analysis of thyroid-inflammatory-autoimmune derangements in patients with AITD.</div></div><div><h3>Results</h3><div>A total of 2,082 COVID-19 patients diagnosed with AITD and 257 cases without AITD were included in the study, and 464 non-COVID-19 patients were supplemented, dividing into 14 AITD and 450 non-AITD cases. We found that COVID-19 infection was closely associated with thyroid dysfunction (<em>χ</em><sup><em>2</em></sup> = 1518.129, <em>p</em> = 0.000). AITD patients with COVID-19 showed a higher prevalence of symptoms and comorbidities and longer hospital stays at baseline than non-AITD patients with COVID-19 (<em>p</em> = 0.000, <em>p</em> = 0.000, and <em>p</em> = 0.000). The baseline free triiodothyronine (FT3), free thyroxine, and radioactive iodine uptake at 24 hours in AITD cases significantly decreased (<em>p</em> = 0.000, <em>p</em> = 0.000, and <em>p</em> = 0.000), while thyroid stimulating hormone, thyroglobulin, reverse triiodothyronine (rT3), and thyroid antibodies varying elevated from the baseline to the follow-up (baseline: <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, and <em>p</em> = 0.000; 3-month follow-up: <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.030, and <em>p</em> = 0.000). C-reactive protein, calcitonin, interleukin-6, -8, -10, and tumor necrosis factor-α rose significantly at baseline (<em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, and <em>p</em> = 0.000) in AITD. Interferon-α and interferon-γ at baseline showed a significant decrease (<em>p</em> = 0.000 and <em>p</em> = 0.000), and remained at low levels after 6 months (<em>p</em> = 0.000 and <em>p</em> = 0.000). FT3 and rT3 were positively and negatively correlated with hospitalization, respectively (<em>r</em> = -0.208, 0.231; <em>p</em> = 0.000, <em>p</em> = 0.000). ROC curves showed that FT3 and rT3 had better robustness in predicting severe COVID-19 prognosis (AUC = 0.801, 0.705). Ordered logistic regression revealed that ORs were
{"title":"Association of COVID-19 with Thyroid Dysfunction and Autoimmune Thyroid Disease: A Retrospective Cohort Study","authors":"Jia Di , Xiaodong Ma , Tao Wu , Eryue Qiao , Mojtaba Salouti , Yu Zhong , Qian Xia , Danfeng Kong , Min Hao , Qingwei Xie , Zhuang Ge , Dongzheng Liu , Juanyi Feng , Xianghong Zheng","doi":"10.1016/j.jtauto.2024.100255","DOIUrl":"10.1016/j.jtauto.2024.100255","url":null,"abstract":"<div><h3>Background</h3><div>Since the end of the COVID-19 pandemic, the potential roles of thyroid-inflammatory derangements in driving or being associated with the prognosis of COVID-19 remain controversial. We aimed to clarify the association between COVID-19 infection and thyroid dysfunction, and highlight the impacts of subsequent autoimmune thyroid disease (AITD) on the prognosis of COVID-19.</div></div><div><h3>Methods</h3><div>The retrospective, multicenter, cohort study enrolled 2,339 participants with COVID-19 from three hospitals located in the north, middle, and south regions of Shaan Xi Province, China, between December 2022 and July 2023. 464 non-COVID-19 patients within the same period were supplemented, divided into groups with and without AITD. At hospital admission (baseline), 3- and 6-month follow-ups, we presented a dynamic description and correlation analysis of thyroid-inflammatory-autoimmune derangements in patients with AITD.</div></div><div><h3>Results</h3><div>A total of 2,082 COVID-19 patients diagnosed with AITD and 257 cases without AITD were included in the study, and 464 non-COVID-19 patients were supplemented, dividing into 14 AITD and 450 non-AITD cases. We found that COVID-19 infection was closely associated with thyroid dysfunction (<em>χ</em><sup><em>2</em></sup> = 1518.129, <em>p</em> = 0.000). AITD patients with COVID-19 showed a higher prevalence of symptoms and comorbidities and longer hospital stays at baseline than non-AITD patients with COVID-19 (<em>p</em> = 0.000, <em>p</em> = 0.000, and <em>p</em> = 0.000). The baseline free triiodothyronine (FT3), free thyroxine, and radioactive iodine uptake at 24 hours in AITD cases significantly decreased (<em>p</em> = 0.000, <em>p</em> = 0.000, and <em>p</em> = 0.000), while thyroid stimulating hormone, thyroglobulin, reverse triiodothyronine (rT3), and thyroid antibodies varying elevated from the baseline to the follow-up (baseline: <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, and <em>p</em> = 0.000; 3-month follow-up: <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.030, and <em>p</em> = 0.000). C-reactive protein, calcitonin, interleukin-6, -8, -10, and tumor necrosis factor-α rose significantly at baseline (<em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, <em>p</em> = 0.000, and <em>p</em> = 0.000) in AITD. Interferon-α and interferon-γ at baseline showed a significant decrease (<em>p</em> = 0.000 and <em>p</em> = 0.000), and remained at low levels after 6 months (<em>p</em> = 0.000 and <em>p</em> = 0.000). FT3 and rT3 were positively and negatively correlated with hospitalization, respectively (<em>r</em> = -0.208, 0.231; <em>p</em> = 0.000, <em>p</em> = 0.000). ROC curves showed that FT3 and rT3 had better robustness in predicting severe COVID-19 prognosis (AUC = 0.801, 0.705). Ordered logistic regression revealed that ORs were","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100255"},"PeriodicalIF":4.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142527347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.jtauto.2024.100253
Daniel Galeano-Sánchez, Victoria Morales-González, Diana M. Monsalve, Carolina Ramırez-Santana, Yeny Acosta-Ampudia
Autoimmune diseases (ADs) are immunological disorders arising from the breakdown of immune tolerance, influenced by various internal and external factors. Persistent exposure to environmental factors, particularly air pollution, is linked to systemic inflammation, oxidative stress, and apoptosis, which contribute to the development of ADs.
This review examines the impact of air pollutants, including particulate matter, silica, and TCDD, by analyzing epidemiological studies, animal models, and in vitro assays. It focuses on how air pollution disrupts the immune system, leading to apoptosis, increased oxidative stress, cytokine production, autoantigen release, autoantibody production, and autoreactivity, which are particularly significant in ADs like rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and systemic sclerosis. In essence, this approach aims to provide a profound understanding of how exposure to air pollution can initiate or contribute to ADs, offering potential avenues for more targeted preventive and therapeutic strategies.
{"title":"Airborne culprits: A comprehensive review of PM, silica, and TCDD in autoimmune diseases","authors":"Daniel Galeano-Sánchez, Victoria Morales-González, Diana M. Monsalve, Carolina Ramırez-Santana, Yeny Acosta-Ampudia","doi":"10.1016/j.jtauto.2024.100253","DOIUrl":"10.1016/j.jtauto.2024.100253","url":null,"abstract":"<div><div>Autoimmune diseases (ADs) are immunological disorders arising from the breakdown of immune tolerance, influenced by various internal and external factors. Persistent exposure to environmental factors, particularly air pollution, is linked to systemic inflammation, oxidative stress, and apoptosis, which contribute to the development of ADs.</div><div>This review examines the impact of air pollutants, including particulate matter, silica, and TCDD, by analyzing epidemiological studies, animal models, and <em>in vitro</em> assays. It focuses on how air pollution disrupts the immune system, leading to apoptosis, increased oxidative stress, cytokine production, autoantigen release, autoantibody production, and autoreactivity, which are particularly significant in ADs like rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and systemic sclerosis. In essence, this approach aims to provide a profound understanding of how exposure to air pollution can initiate or contribute to ADs, offering potential avenues for more targeted preventive and therapeutic strategies.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100253"},"PeriodicalIF":4.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B cells play a major role in the development and maintenance of systemic lupus erythematosus (SLE). Double negative (DN) B cells defined by the lack of surface expression of IgD and CD27 have attracted recent interest for their sensitivity to Toll-like receptor 7 (TLR7) ligands and their potential role in the production of autoantibodies. Here we aimed at investigating the possible association of DN B cells and their subsets with SLE disease activity specifically in female patients, in which TLR7 gene has been reported to escape X chromosome inactivation.
Methods
Peripheral blood mononuclear cells were purified from woman participating to the clinically well-characterized Swiss SLE Cohort Study (SSCS). PBMC from age-matched healthy females were used as controls. PBMC were stained for cell surface markers, intracellular Tbet and analyzed by multicolor cytofluorimetry. Single nucleotide TLR7 polymorphisms were assessed by polymerase chain reaction.
Results
The median SLE disease activity index of the 86 females was 2, IQR [0–6], all but 8 were under chronic SLE treatment. B cells co-expressing CD11c and Tbet were increased, the mean fluorescence intensity (MFI) of CD19 was considerably reduced and we observed a large increase in CD11c + CXCR5-and CD11c-CXCR5-concomitantly with a reduction of CD11c-CXCR5+ B cells in SLE compared to 40 healthy donors (HD). When focusing on the DN B cell subset, we found a reduction of DN1 (CD11c-CXCR5+) and an increase of DN2 (CD11c + CXCR5-) and most impressively of DN3 (CD11c-CXCR5-) cells. The DN subset, particularly DN3, showed the lowest level of CD19 expression. Both DN1 and DN3 percentages as well as the CD19 MFI of DN cells were associated with SLE disease activity. The use of glucocorticoids, immunosuppressants, and antimalarials impacted differentially on the frequencies of DN B cell subsets. CD19 MFI in B cells and the percentage of DN3 were the strongest biomarkers of disease activity. The TLR7 snp3858384 G allele was associated with increased percentages of B cells and CD19+CD11c-CXCR5+ and decreased CD19+CD11c-CXCR5-.
Conclusions
DN3 B cells are strongly associated with SLE clinical activity pointing to their potential involvement in disease pathogenesis, and CD19 expression level performs accurately as disease activity biomarker.
{"title":"Extrafollicular CD19lowCXCR5−CD11c− double negative 3 (DN3) B cells are significantly associated with disease activity in females with systemic lupus erythematosus","authors":"Carlo Chizzolini , Jean-Charles Guery , Fanny Noulet , Lyssia Gruaz , Claire Cenac , Loredana Frasca , David Spoerl , Lionel Arlettaz , Alice Horisberger , Camillo Ribi , Stéphanie Hugues","doi":"10.1016/j.jtauto.2024.100252","DOIUrl":"10.1016/j.jtauto.2024.100252","url":null,"abstract":"<div><h3>Objective</h3><div>B cells play a major role in the development and maintenance of systemic lupus erythematosus (SLE). Double negative (DN) B cells defined by the lack of surface expression of IgD and CD27 have attracted recent interest for their sensitivity to Toll-like receptor 7 (TLR7) ligands and their potential role in the production of autoantibodies. Here we aimed at investigating the possible association of DN B cells and their subsets with SLE disease activity specifically in female patients, in which TLR7 gene has been reported to escape X chromosome inactivation.</div></div><div><h3>Methods</h3><div>Peripheral blood mononuclear cells were purified from woman participating to the clinically well-characterized Swiss SLE Cohort Study (SSCS). PBMC from age-matched healthy females were used as controls. PBMC were stained for cell surface markers, intracellular Tbet and analyzed by multicolor cytofluorimetry. Single nucleotide TLR7 polymorphisms were assessed by polymerase chain reaction.</div></div><div><h3>Results</h3><div>The median SLE disease activity index of the 86 females was 2, IQR [0–6], all but 8 were under chronic SLE treatment. B cells co-expressing CD11c and Tbet were increased, the mean fluorescence intensity (MFI) of CD19 was considerably reduced and we observed a large increase in CD11c + CXCR5-and CD11c-CXCR5-concomitantly with a reduction of CD11c-CXCR5+ B cells in SLE compared to 40 healthy donors (HD). When focusing on the DN B cell subset, we found a reduction of DN1 (CD11c-CXCR5+) and an increase of DN2 (CD11c + CXCR5-) and most impressively of DN3 (CD11c-CXCR5-) cells. The DN subset, particularly DN3, showed the lowest level of CD19 expression. Both DN1 and DN3 percentages as well as the CD19 MFI of DN cells were associated with SLE disease activity. The use of glucocorticoids, immunosuppressants, and antimalarials impacted differentially on the frequencies of DN B cell subsets. CD19 MFI in B cells and the percentage of DN3 were the strongest biomarkers of disease activity. The TLR7 snp3858384 G allele was associated with increased percentages of B cells and CD19<sup>+</sup>CD11c-CXCR5+ and decreased CD19<sup>+</sup>CD11c-CXCR5-.</div></div><div><h3>Conclusions</h3><div>DN3 B cells are strongly associated with SLE clinical activity pointing to their potential involvement in disease pathogenesis, and CD19 expression level performs accurately as disease activity biomarker.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100252"},"PeriodicalIF":4.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1016/j.jtauto.2024.100251
Mingzhu Liu , Xiongquan Long , Shuangshuang Fu , Yuyang Zhang , Zihao Liu , Xiaoping Xu , Minghao Wu
Background
Mitochondrial DNA plays a crucial role in the pathophysiology of autoimmune diseases (ADs). However, the association between mitochondrial DNA copy number (mtDNA-CN) and ADs risk is controversial. In this study, Mendelian randomization (MR) analysis and meta-analysis were performed using three sets of independent instrumental variables (IVs) to investigate the potential association between mtDNA-CN and 20 types of ADs.
Methods
The three sets of IVs were drawn primarily from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. Outcome data for ADs were investigated using summary statistics from the FinnGen cohort. The potential causal associations were assessed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. Sensitivity analysis and the Steiger test were used to verify the robustness of the MR estimates. In addition, a meta-analysis was conducted to pool the results from three IV groups.
Results
Overall, genetically predicted mtDNA-CN was not associated with ADs risk (OR = 1.046, 95 % CI: 0.964–1.135, P = 0.283). However, subgroup analyses showed positive causal associations of mtDNA-CN with autoimmune hypothyroidism (OR = 1.133, 95 % CI: 1.016–1.262, P = 0.024) and rheumatoid arthritis (OR = 1.219, 95 % CI: 1.028–1.445, P = 0.023). In contrast, there was no causal association between mtDNA-CN and atopic dermatitis as well as psoriasis, ulcerative colitis, adult-onset Still disease, type1 diabetes, Crohn disease, sarcoidosis, ankylosing spondylitis, multiple sclerosis, autoimmune hyperthyroidism, primary sclerosing cholangitis, systemic lupus erythematosus, systemic sclerosis, alopecia areata, myasthenia gravis, Guillain-Barre syndrome, dermatopolymyositis, and vitiligo.
Conclusions
This MR analysis showed mtDNA-CN is causally associated with an increased risk of autoimmune hypothyroidism and rheumatoid arthritis at the genetic level. The findings have important implications for the use of mtDNA-CN as a biomarker for risk assessment of autoimmune hypothyroidism and rheumatoid arthritis in clinical practice.
{"title":"Mitochondrial DNA copy number and the risk of autoimmune diseases: A Mendelian randomization study with meta-analysis","authors":"Mingzhu Liu , Xiongquan Long , Shuangshuang Fu , Yuyang Zhang , Zihao Liu , Xiaoping Xu , Minghao Wu","doi":"10.1016/j.jtauto.2024.100251","DOIUrl":"10.1016/j.jtauto.2024.100251","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial DNA plays a crucial role in the pathophysiology of autoimmune diseases (ADs). However, the association between mitochondrial DNA copy number (mtDNA-CN) and ADs risk is controversial. In this study, Mendelian randomization (MR) analysis and meta-analysis were performed using three sets of independent instrumental variables (IVs) to investigate the potential association between mtDNA-CN and 20 types of ADs.</div></div><div><h3>Methods</h3><div>The three sets of IVs were drawn primarily from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. Outcome data for ADs were investigated using summary statistics from the FinnGen cohort. The potential causal associations were assessed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. Sensitivity analysis and the Steiger test were used to verify the robustness of the MR estimates. In addition, a meta-analysis was conducted to pool the results from three IV groups.</div></div><div><h3>Results</h3><div>Overall, genetically predicted mtDNA-CN was not associated with ADs risk (OR = 1.046, 95 % CI: 0.964–1.135, P = 0.283). However, subgroup analyses showed positive causal associations of mtDNA-CN with autoimmune hypothyroidism (OR = 1.133, 95 % CI: 1.016–1.262, P = 0.024) and rheumatoid arthritis (OR = 1.219, 95 % CI: 1.028–1.445, P = 0.023). In contrast, there was no causal association between mtDNA-CN and atopic dermatitis as well as psoriasis, ulcerative colitis, adult-onset Still disease, type1 diabetes, Crohn disease, sarcoidosis, ankylosing spondylitis, multiple sclerosis, autoimmune hyperthyroidism, primary sclerosing cholangitis, systemic lupus erythematosus, systemic sclerosis, alopecia areata, myasthenia gravis, Guillain-Barre syndrome, dermatopolymyositis, and vitiligo.</div></div><div><h3>Conclusions</h3><div>This MR analysis showed mtDNA-CN is causally associated with an increased risk of autoimmune hypothyroidism and rheumatoid arthritis at the genetic level. The findings have important implications for the use of mtDNA-CN as a biomarker for risk assessment of autoimmune hypothyroidism and rheumatoid arthritis in clinical practice.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100251"},"PeriodicalIF":4.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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