Pub Date : 2024-02-15DOI: 10.1016/j.jtauto.2024.100234
Mingming Zhang , Zhuye Qin , Yexi Huang , Wenyan Tian , You Li , Chan Wang , Weifeng Zhao , Yaping Dai , Xingjuan Shi , M. Eric Gershwin , Xiong Ma , Meilin Wang , Xiangdong Liu , Weichang Chen , Fang Qiu
The biliary epithelial cells release CC chemokine receptor 6 (CCR6) ligand 20 (CCL20), leading to recruitment of CCR6+ T cells and subsequent infiltration into the biliary epithelium in primary biliary cholangitis patients. Previous genome-wide multi-national meta-analysis, including our Han Chinese cohort, showed significant association of CCR6 and CCL20 single nucleotide polymorphisms (SNP) with PBC. We report here that significantly associated SNPs, identified in the CCR6 locus based on our Han Chinese genome-wide association study, can be separated into “protective” and “risk” groups, but only “risk” SNPs were confirmed using a separate Han Chinese PBC cohort. Only weak association of CCL20 SNPs was observed in Han Chinese PBC cohorts. Fine-mapping and logistical analysis identified a previously defined functional variant that, leads to increased CCR6 expression, which contributed to increased genetic susceptibility to PBC in Han Chinese cohort.
{"title":"Association of CCR6 functional polymorphisms with Primary Biliary Cholangitis","authors":"Mingming Zhang , Zhuye Qin , Yexi Huang , Wenyan Tian , You Li , Chan Wang , Weifeng Zhao , Yaping Dai , Xingjuan Shi , M. Eric Gershwin , Xiong Ma , Meilin Wang , Xiangdong Liu , Weichang Chen , Fang Qiu","doi":"10.1016/j.jtauto.2024.100234","DOIUrl":"10.1016/j.jtauto.2024.100234","url":null,"abstract":"<div><p>The biliary epithelial cells release CC chemokine receptor 6 (<em>CCR6</em>) ligand 20 (<em>CCL20</em>), leading to recruitment of CCR6<sup>+</sup> T cells and subsequent infiltration into the biliary epithelium in primary biliary cholangitis patients. Previous genome-wide multi-national meta-analysis, including our Han Chinese cohort, showed significant association of <em>CCR6</em> and <em>CCL20</em> single nucleotide polymorphisms (SNP) with PBC. We report here that significantly associated SNPs, identified in the <em>CCR6</em> locus based on our Han Chinese genome-wide association study, can be separated into “protective” and “risk” groups, but only “risk” SNPs were confirmed using a separate Han Chinese PBC cohort. Only weak association of <em>CCL20</em> SNPs was observed in Han Chinese PBC cohorts. Fine-mapping and logistical analysis identified a previously defined functional variant that, leads to increased <em>CCR6</em> expression, which contributed to increased genetic susceptibility to PBC in Han Chinese cohort.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100234"},"PeriodicalIF":3.9,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000042/pdfft?md5=bde0fac6bd5f49d1477123acbe1d46a0&pid=1-s2.0-S2589909024000042-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139824762","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 : 2024-01-07DOI: 10.1016/j.jtauto.2024.100231
Solveig Skovlund Groen , Anne-Christine Bay-Jensen , Christian S. Thudium , Morten H. Dziegiel , Marie Skougaard , Simon Francis Thomsen , Signe Holm Nielsen
<div><h3>Introduction</h3><p>T-helper 17 (Th17) cells produce IL-17A playing a critical role in activating the pathogenic chain leading to joint tissue inflammation and destruction. Elevated levels of Th17 cells and IL-17A have been detected in skin lesions, blood, and synovial fluid from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Moreover, IL-17A inhibitors suppress disease activity in psoriasis, PsA and AS, supporting the evidence of IL-17A contributing to the disease pathogenesis. Although, IL-17A inhibitors are widely approved, it remains unclear how the inhibitory effect of IL-17A alters the extracellular matrix (ECM) of the joint in a Th17-conditioned inflammatory milieu. Therefore, the aim of this study was to establish a cartilage model cultured with conditioned medium from Th17 cells and inhibitors to explore the effect of IL-17A inhibition on joint tissue remodeling.</p></div><div><h3>Methods</h3><p>Naïve CD4<sup>+</sup> T cells from healthy human buffy coat were differentiated into Th17 cells, followed by Th17 cell activation to secrete Th17-related cytokines and molecules into media. The activated Th17 cells were isolated from the conditioned media (CM) and analyzed using flow cytometry to verify Th17 cell differentiation. The CM were assessed with ELISA to quantify the concentrations of cytokines secreted into the media by the Th17 cells. Healthy bovine cartilage explants were cultured with the Th17-CM and treated with IL-17A and TNFα inhibitors for 21 days. In harvested supernatant from the cartilage cultures, MMP- and ADAMTS-mediated biomarker fragments of type II collagen, aggrecan, and fibronectin were measured by ELISA to investigate the ECM remodeling within the cartilage tissue.</p></div><div><h3>Results</h3><p>Th17-CM stimulated a catabolic response in the cartilage. Markers of type II collagen and aggrecan degradation were upregulated, while anabolic marker of type II collagen formation remained on similar levels as the untreated explants. The addition of IL-17A inhibitor to Th17-CM decreased the elevated type II collagen and aggrecan degradation, however, degenerative levels were still elevated compared to untreated group. The addition of TNFα inhibitor completely reduced both type II collagen and aggrecan degradation compared to untreated explants. Moreover, the TNFα inhibitor treatment did not alter the type II collagen formation compared to untreated group.</p></div><div><h3>Conclusion</h3><p>This study suggests that inhibition of IL-17A in Th17-conditioned cartilage tissue only partially reduced the MMP-mediated type II collagen degradation and ADAMTS-mediated aggrecan degradation, while the TNFα inhibitor treatment fully reduced both MMP- and ADAMTS-mediated ECM degradation. This exploratory study where ECM biomarkers are combined with Th17-conditioned <em>ex vivo</em> model may hold great potential as output for describing joint disease mechanisms and predicting structural effects of trea
{"title":"Evaluating the inhibition of IL-17A and TNFα in a cartilage explant model cultured with Th17-derived cytokines","authors":"Solveig Skovlund Groen , Anne-Christine Bay-Jensen , Christian S. Thudium , Morten H. Dziegiel , Marie Skougaard , Simon Francis Thomsen , Signe Holm Nielsen","doi":"10.1016/j.jtauto.2024.100231","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100231","url":null,"abstract":"<div><h3>Introduction</h3><p>T-helper 17 (Th17) cells produce IL-17A playing a critical role in activating the pathogenic chain leading to joint tissue inflammation and destruction. Elevated levels of Th17 cells and IL-17A have been detected in skin lesions, blood, and synovial fluid from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Moreover, IL-17A inhibitors suppress disease activity in psoriasis, PsA and AS, supporting the evidence of IL-17A contributing to the disease pathogenesis. Although, IL-17A inhibitors are widely approved, it remains unclear how the inhibitory effect of IL-17A alters the extracellular matrix (ECM) of the joint in a Th17-conditioned inflammatory milieu. Therefore, the aim of this study was to establish a cartilage model cultured with conditioned medium from Th17 cells and inhibitors to explore the effect of IL-17A inhibition on joint tissue remodeling.</p></div><div><h3>Methods</h3><p>Naïve CD4<sup>+</sup> T cells from healthy human buffy coat were differentiated into Th17 cells, followed by Th17 cell activation to secrete Th17-related cytokines and molecules into media. The activated Th17 cells were isolated from the conditioned media (CM) and analyzed using flow cytometry to verify Th17 cell differentiation. The CM were assessed with ELISA to quantify the concentrations of cytokines secreted into the media by the Th17 cells. Healthy bovine cartilage explants were cultured with the Th17-CM and treated with IL-17A and TNFα inhibitors for 21 days. In harvested supernatant from the cartilage cultures, MMP- and ADAMTS-mediated biomarker fragments of type II collagen, aggrecan, and fibronectin were measured by ELISA to investigate the ECM remodeling within the cartilage tissue.</p></div><div><h3>Results</h3><p>Th17-CM stimulated a catabolic response in the cartilage. Markers of type II collagen and aggrecan degradation were upregulated, while anabolic marker of type II collagen formation remained on similar levels as the untreated explants. The addition of IL-17A inhibitor to Th17-CM decreased the elevated type II collagen and aggrecan degradation, however, degenerative levels were still elevated compared to untreated group. The addition of TNFα inhibitor completely reduced both type II collagen and aggrecan degradation compared to untreated explants. Moreover, the TNFα inhibitor treatment did not alter the type II collagen formation compared to untreated group.</p></div><div><h3>Conclusion</h3><p>This study suggests that inhibition of IL-17A in Th17-conditioned cartilage tissue only partially reduced the MMP-mediated type II collagen degradation and ADAMTS-mediated aggrecan degradation, while the TNFα inhibitor treatment fully reduced both MMP- and ADAMTS-mediated ECM degradation. This exploratory study where ECM biomarkers are combined with Th17-conditioned <em>ex vivo</em> model may hold great potential as output for describing joint disease mechanisms and predicting structural effects of trea","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100231"},"PeriodicalIF":3.9,"publicationDate":"2024-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000017/pdfft?md5=61ffc6f0ec57f666cac3c55f9b5c7838&pid=1-s2.0-S2589909024000017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139436568","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 : 2023-12-24DOI: 10.1016/j.jtauto.2023.100230
Yijiao Xu , Lumin Wang , Zhisheng Chen , Qingwei Zhang , Yun Shen , Yanrong Ye , Jiaxin Liu , Huijun Zhang
Thymoma with Immunodeficiency (Good's Syndrome, GS) is a rare association between thymoma and immunodeficiency, first described over 60 years ago. Patients with GS typically present with thymomas, reduced or absent B cells in the peripheral blood, hypogammaglobulinemia, and defects in cell-mediated immunity. We report the case of a 67-year-old woman diagnosed with GS following the development of a progressive, severe, refractory pulmonary infection and diffuse panbronchiolitis (DPB). She also had diabetes, characterized by anti-glutamic acid decarboxylase antibody positivity, leading to a diagnosis of latent autoimmune diabetes in adults (LADA). A thorough review of existing literature revealed that GS is often confirmed after multiple episodes of opportunistic infections or autoimmune diseases post-thymoma surgery. Due to their immunodeficiency, GS patients frequently suffer from recurrent infections over extended periods, and some succumb to severe infections. Regular immunoglobulin infusions may be effective in treating GS.
{"title":"Thymoma with immunodeficiency, combined diffuse panbronchiolitis, and latent autoimmune diabetes in adults- case report and systematic review","authors":"Yijiao Xu , Lumin Wang , Zhisheng Chen , Qingwei Zhang , Yun Shen , Yanrong Ye , Jiaxin Liu , Huijun Zhang","doi":"10.1016/j.jtauto.2023.100230","DOIUrl":"https://doi.org/10.1016/j.jtauto.2023.100230","url":null,"abstract":"<div><p>Thymoma with Immunodeficiency (Good's Syndrome, GS) is a rare association between thymoma and immunodeficiency, first described over 60 years ago. Patients with GS typically present with thymomas, reduced or absent B cells in the peripheral blood, hypogammaglobulinemia, and defects in cell-mediated immunity. We report the case of a 67-year-old woman diagnosed with GS following the development of a progressive, severe, refractory pulmonary infection and diffuse panbronchiolitis (DPB). She also had diabetes, characterized by anti-glutamic acid decarboxylase antibody positivity, leading to a diagnosis of latent autoimmune diabetes in adults (LADA). A thorough review of existing literature revealed that GS is often confirmed after multiple episodes of opportunistic infections or autoimmune diseases post-thymoma surgery. Due to their immunodeficiency, GS patients frequently suffer from recurrent infections over extended periods, and some succumb to severe infections. Regular immunoglobulin infusions may be effective in treating GS.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100230"},"PeriodicalIF":3.9,"publicationDate":"2023-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909023000436/pdfft?md5=e058759fb69c79be34e773d370a73337&pid=1-s2.0-S2589909023000436-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139041218","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 : 2023-12-21DOI: 10.1016/j.jtauto.2023.100228
Shi Zhang , Yao Liu , Xiao-Long Zhang , Yun Sun , Zhong-Hua Lu
Acute respiratory distress syndrome (ARDS) is independently associated with a poor prognosis in patients with sepsis. Macrophage M1 polarization plays an instrumental role in this process. Therefore, the exploration of key molecules affecting acute lung injury and macrophage M1 polarization may provide therapeutic targets for the treatment of septic ARDS. Here, we identified that elevated levels of Ankyrin repeat domain-containing protein 22 (ANKRD22) were associated with poor prognosis and more pronounced M1 macrophage polarization in septic patients by analyzing high-throughput data. ANKRD22 expression was also significantly upregulated in the alveolar lavage fluid, peripheral blood, and lung tissue of septic ARDS model mice. Knockdown of ANKRD22 significantly attenuated acute lung injury in mice with sepsis-induced ARDS and reduced the M1 polarization of lung macrophages. Furthermore, deletion of ANKRD22 in macrophages inhibited M1 macrophage polarization and reduced levels of phosphorylated IRF3 and intracellular interferon regulatory factor 3 (IRF3) expression, while re-expression of ANKRD22 reversed these changes. Further experiments revealed that ANKRD22 promotes IRF3 activation by binding to mitochondrial antiviral-signaling protein (MAVS). In conclusion, these findings suggest that ANKRD22 promotes the M1 polarization of lung macrophages and exacerbates sepsis-induced ARDS.
{"title":"ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization","authors":"Shi Zhang , Yao Liu , Xiao-Long Zhang , Yun Sun , Zhong-Hua Lu","doi":"10.1016/j.jtauto.2023.100228","DOIUrl":"10.1016/j.jtauto.2023.100228","url":null,"abstract":"<div><p>Acute respiratory distress syndrome (ARDS) is independently associated with a poor prognosis in patients with sepsis. Macrophage M1 polarization plays an instrumental role in this process. Therefore, the exploration of key molecules affecting acute lung injury and macrophage M1 polarization may provide therapeutic targets for the treatment of septic ARDS. Here, we identified that elevated levels of Ankyrin repeat domain-containing protein 22 (ANKRD22) were associated with poor prognosis and more pronounced M1 macrophage polarization in septic patients by analyzing high-throughput data. ANKRD22 expression was also significantly upregulated in the alveolar lavage fluid, peripheral blood, and lung tissue of septic ARDS model mice. Knockdown of ANKRD22 significantly attenuated acute lung injury in mice with sepsis-induced ARDS and reduced the M1 polarization of lung macrophages. Furthermore, deletion of ANKRD22 in macrophages inhibited M1 macrophage polarization and reduced levels of phosphorylated IRF3 and intracellular interferon regulatory factor 3 (IRF3) expression, while re-expression of ANKRD22 reversed these changes. Further experiments revealed that ANKRD22 promotes IRF3 activation by binding to mitochondrial antiviral-signaling protein (MAVS). In conclusion, these findings suggest that ANKRD22 promotes the M1 polarization of lung macrophages and exacerbates sepsis-induced ARDS.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100228"},"PeriodicalIF":3.9,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909023000412/pdfft?md5=92cf84ecd305ce892f8bc331cdac5b55&pid=1-s2.0-S2589909023000412-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138986392","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 : 2023-12-21DOI: 10.1016/j.jtauto.2023.100226
Chumei Zeng , Huiying Liu , Zilian Wang , Jingting Li
Background
The relationship between genetic immune dysregulation and the occurrence of preeclampsia (PE) or PE with fetal growth restriction (PE with FGR) has yielded inconsistent findings, and the underlying mediators of this association remain elusive. We aimed to explore the causal impact of genetic immune dysregulation on the risk of PE or PE with FGR and to elucidate the role of specific transcriptomes in mediating this relationship.
Methods
A two-step Mendelian randomization (MR) analysis was performed to explore the link between immune dysregulation and PE or PE with FGR, as well as to identify potential inflammatory biomarkers that act as mediators. GWAS summary data for outcomes were obtained from the FinnGen dataset. The analyses encompassed five systemic immune-associated diseases, four chronic genital inflammatory diseases, and thirty-one inflammatory biomarkers. Summary-data-based MR (SMR) and HEIDI analysis were conducted to test whether the effect size of single nucleotide polymorphisms (SNPs) on outcomes was mediated by the expression of immune-associated genes.
Results
The primary univariable analysis revealed a significant positive correlation between systemic lupus erythematosus (SLE), type 1 diabetes (T1D), type 2 diabetes (T2D), and rheumatoid arthritis (RA) with the risk of PE or PE with FGR. Surprisingly, a counterintuitive finding showed a significant negative association between endometriosis of pelvic peritoneum (EMoP) and the risk of PE with FGR. None of the inflammatory factors had a causal relationship with PE or PE with FGR. However, there was a significant association between lymphocyte count and the risk of PE with FGR. Within the lymphocyte subset, both the proportion of Natural Killer (NK) cells and absolute counts of naïve CD4+ T cells demonstrated significant effects on the risk of PE with FGR. Two-step MR analysis underscored the genetically predicted lymphocyte count as a significant mediator between T1D and PE with FGR. Additionally, SMR analysis indicated the potential involvement of SH2B3 in the occurrence of PE with FGR.
Conclusions
Our findings provided substantial evidence of the underlying causal relationship between immune dysregulation and PE or PE with FGR and some of these diseases proved to accelerate immune cells disorders and then contribute to the risk of incident PE or PE with FGR.
背景遗传性免疫失调与子痫前期(PE)或子痫伴胎儿生长受限(PE with FGR)的发生之间的关系得出了不一致的研究结果,而这种关联的潜在中介因素仍然难以捉摸。我们的目的是探讨遗传性免疫失调对子痫或子痫合并 FGR 风险的因果影响,并阐明特定转录组在介导这种关系中的作用。方法进行了两步孟德尔随机化(MR)分析,以探讨免疫失调与子痫或子痫合并 FGR 之间的联系,并确定作为介导因素的潜在炎症生物标志物。结果的 GWAS 总结数据来自 FinnGen 数据集。分析包括五种全身性免疫相关疾病、四种慢性生殖器炎症疾病和 31 种炎症生物标志物。结果主要的单变量分析显示,系统性红斑狼疮(SLE)、1 型糖尿病(T1D)、2 型糖尿病(T2D)和类风湿性关节炎(RA)与 PE 或 PE 伴 FGR 的风险之间存在显著的正相关。令人惊讶的是,一个反直觉的发现表明,盆腔腹膜子宫内膜异位症(EMoP)与妊娠合并胎儿畸形的风险呈显著负相关。没有一个炎症因素与 PE 或 PE 合并绒毛膜促性腺激素有因果关系。然而,淋巴细胞计数与妊娠合并先天性子宫发育不良的风险有明显关系。在淋巴细胞亚群中,自然杀伤(NK)细胞的比例和幼稚CD4+T细胞的绝对计数对妊娠合并FGR的风险都有显著影响。两步 MR 分析强调了基因预测的淋巴细胞数量是 T1D 和胎儿绒毛膜促性腺激素性肝炎之间的重要中介因素。此外,SMR 分析表明 SH2B3 可能参与了妊娠合并绒毛膜促性腺激素增多症的发生。结论我们的研究结果提供了大量证据,证明免疫失调与妊娠合并绒毛膜促性腺激素增多症或妊娠合并绒毛膜促性腺激素增多症之间存在潜在的因果关系,其中一些疾病被证明会加速免疫细胞失调,进而导致妊娠合并绒毛膜促性腺激素增多症或妊娠合并绒毛膜促性腺激素增多症的发病风险。
{"title":"Novel insights into the complex interplay of immune dysregulation and inflammatory biomarkers in preeclampsia and fetal growth restriction: A two-step Mendelian randomization analysis","authors":"Chumei Zeng , Huiying Liu , Zilian Wang , Jingting Li","doi":"10.1016/j.jtauto.2023.100226","DOIUrl":"https://doi.org/10.1016/j.jtauto.2023.100226","url":null,"abstract":"<div><h3>Background</h3><p>The relationship between genetic immune dysregulation and the occurrence of preeclampsia (PE) or PE with fetal growth restriction (PE with FGR) has yielded inconsistent findings, and the underlying mediators of this association remain elusive. We aimed to explore the causal impact of genetic immune dysregulation on the risk of PE or PE with FGR and to elucidate the role of specific transcriptomes in mediating this relationship.</p></div><div><h3>Methods</h3><p>A two-step Mendelian randomization (MR) analysis was performed to explore the link between immune dysregulation and PE or PE with FGR, as well as to identify potential inflammatory biomarkers that act as mediators. GWAS summary data for outcomes were obtained from the FinnGen dataset. The analyses encompassed five systemic immune-associated diseases, four chronic genital inflammatory diseases, and thirty-one inflammatory biomarkers. Summary-data-based MR (SMR) and HEIDI analysis were conducted to test whether the effect size of single nucleotide polymorphisms (SNPs) on outcomes was mediated by the expression of immune-associated genes.</p></div><div><h3>Results</h3><p>The primary univariable analysis revealed a significant positive correlation between systemic lupus erythematosus (SLE), type 1 diabetes (T1D), type 2 diabetes (T2D), and rheumatoid arthritis (RA) with the risk of PE or PE with FGR. Surprisingly, a counterintuitive finding showed a significant negative association between endometriosis of pelvic peritoneum (EMoP) and the risk of PE with FGR. None of the inflammatory factors had a causal relationship with PE or PE with FGR. However, there was a significant association between lymphocyte count and the risk of PE with FGR. Within the lymphocyte subset, both the proportion of Natural Killer (NK) cells and absolute counts of naïve CD4<sup>+</sup> T cells demonstrated significant effects on the risk of PE with FGR. Two-step MR analysis underscored the genetically predicted lymphocyte count as a significant mediator between T1D and PE with FGR. Additionally, SMR analysis indicated the potential involvement of SH2B3 in the occurrence of PE with FGR.</p></div><div><h3>Conclusions</h3><p>Our findings provided substantial evidence of the underlying causal relationship between immune dysregulation and PE or PE with FGR and some of these diseases proved to accelerate immune cells disorders and then contribute to the risk of incident PE or PE with FGR.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100226"},"PeriodicalIF":3.9,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909023000394/pdfft?md5=cb5e3031edeced63939855c6ddbaa1b3&pid=1-s2.0-S2589909023000394-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139033830","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 : 2023-12-20DOI: 10.1016/j.jtauto.2023.100225
Jiaqi Zhao , Fangxiao Liu , Lingshuo Bai , Zheng Jiao , Zihui Meng , Bo Jia , Yu Huang , Lin Liu
Background
Patients with ulcerative colitis (UC) often exhibit susceptibilities to multiple autoimmune diseases such as Sjogren's syndrome, primary sclerosing cholangitis, systemic lupus erythematosus, and insulin-dependent diabetes mellitus. This propensity likely stems from common pathogenic mechanisms underlying immune-mediated conditions. This report highlights the occurrence of autoimmune thyroid disease during UC exacerbations. Notably, the patient displayed petrified auricles.
Case Summary.
A 57-year-old male complained of sustained abdominal pain, diarrhea, hematochezia, and mucus for a duration of 20 days. The diagnosis of UC was confirmed via colonoscopy, histopathological examination, and small bowel MRE. Clinical evaluations revealed bilateral ectopic ossification in his ears, which appeared to develop over an unspecified timeframe. Imaging and histological evaluations substantiated the ectopic ossification diagnosis while eliminating the possibility of adrenal insufficiency. The presented case offers a unique instance of bilateral auricular ossification, which is hypothesized to result from hyperthyroidism.
Conclusion
Our case report underscores the necessity of enhancing awareness of the rare complications associated with UC. Medical practitioners should recognize the potential overlap of autoimmune thyroid disorders in UC patients. It is imperative to test for thyroid-related antibodies in such individuals, irrespective of overt thyroid dysfunction.
{"title":"Ulcerative colitis with autoimmune thyroid disease results in bilateral auricular ossificans:a case","authors":"Jiaqi Zhao , Fangxiao Liu , Lingshuo Bai , Zheng Jiao , Zihui Meng , Bo Jia , Yu Huang , Lin Liu","doi":"10.1016/j.jtauto.2023.100225","DOIUrl":"10.1016/j.jtauto.2023.100225","url":null,"abstract":"<div><h3>Background</h3><p>Patients with ulcerative colitis (UC) often exhibit susceptibilities to multiple autoimmune diseases such as Sjogren's syndrome, primary sclerosing cholangitis, systemic lupus erythematosus, and insulin-dependent diabetes mellitus. This propensity likely stems from common pathogenic mechanisms underlying immune-mediated conditions. This report highlights the occurrence of autoimmune thyroid disease during UC exacerbations. Notably, the patient displayed petrified auricles.</p><p>Case Summary.</p><p>A 57-year-old male complained of sustained abdominal pain, diarrhea, hematochezia, and mucus for a duration of 20 days. The diagnosis of UC was confirmed via colonoscopy, histopathological examination, and small bowel MRE. Clinical evaluations revealed bilateral ectopic ossification in his ears, which appeared to develop over an unspecified timeframe. Imaging and histological evaluations substantiated the ectopic ossification diagnosis while eliminating the possibility of adrenal insufficiency. The presented case offers a unique instance of bilateral auricular ossification, which is hypothesized to result from hyperthyroidism.</p></div><div><h3>Conclusion</h3><p>Our case report underscores the necessity of enhancing awareness of the rare complications associated with UC. Medical practitioners should recognize the potential overlap of autoimmune thyroid disorders in UC patients. It is imperative to test for thyroid-related antibodies in such individuals, irrespective of overt thyroid dysfunction.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100225"},"PeriodicalIF":3.9,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909023000382/pdfft?md5=974b0c6db587f329ff0226c4277fe947&pid=1-s2.0-S2589909023000382-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139015912","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 : 2023-12-12DOI: 10.1016/j.jtauto.2023.100227
Saisai Huang , Xiaolei Ma , Juan Cao , Mengru Du , Zhiling Zhao , Dandan Wang , Xue Xu , Jun Liang , Lingyun Sun
The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID‐19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic.
{"title":"Effect of traditional therapeutics on prevalence and clinical outcomes of coronavirus disease 2019 in Chinese patients with autoimmune diseases","authors":"Saisai Huang , Xiaolei Ma , Juan Cao , Mengru Du , Zhiling Zhao , Dandan Wang , Xue Xu , Jun Liang , Lingyun Sun","doi":"10.1016/j.jtauto.2023.100227","DOIUrl":"https://doi.org/10.1016/j.jtauto.2023.100227","url":null,"abstract":"<div><p>The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID‐19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100227"},"PeriodicalIF":3.9,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909023000400/pdfft?md5=c2b9a4279f81df0671e4b84d2422822a&pid=1-s2.0-S2589909023000400-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138656225","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 : 2023-12-01DOI: 10.1016/j.jtauto.2023.100222
Elliott Van Regemorter , Giulia Zorzi , Anais Scohy , Damien Gruson , Johann Morelle
Background and objective
Coronavirus Disease 2019 (COVID-19) has been associated with the onset of autoimmune conditions, but whether this relationship is causal remains unknown, partly because robust evidence based on the detection of autoantibodies is lacking. This study explored the potential impact of COVID-19 pandemic on the temporal trends of autoimmunity.
Methods
Retrospective analysis of all consecutive autoimmune tests performed at one central laboratory at a University hospital, operating services for 18 other hospitals and clinical laboratories in Belgium, from January 01, 2015 to May 31, 2022. Longitudinal changes in the positivity rates of autoimmunity tests were analyzed, i.e. before and after the onset of the COVID-19 pandemic (March 11, 2020). The tests notably included the detection of autoantibodies associated with type 1 diabetes, thyroid diseases, connective tissue diseases, antiphospholipid syndrome, vasculitis and other organ-specific conditions. Kendall rank correlation test was applied to assess temporal trends.
Results
Over a period of 89 months, a total of 301,720 consecutive tests for 24 different autoantibodies among 87,674 unique patients were performed (87% adults, 68% women, mean age 44 ± 20 years). Overall, 52,862 (18%) tests returned positive, with positivity rates for each test ranging between 1% and 46%. No increase in the positivity rate of autoimmunity tests was observed after the start of the pandemic.
Conclusion
The onset of the COVID-19 pandemic was not associated with increased positivity rates of a large panel of autoimmune tests. Whether the higher incidence of autoimmune disorders associated with COVID-19 reflects detection bias or reverse causality, or is linked to seronegative autoimmune disorders requires further investigation.
{"title":"Impact of the COVID-19 pandemic on temporal trends of biological indicators of autoimmunity","authors":"Elliott Van Regemorter , Giulia Zorzi , Anais Scohy , Damien Gruson , Johann Morelle","doi":"10.1016/j.jtauto.2023.100222","DOIUrl":"https://doi.org/10.1016/j.jtauto.2023.100222","url":null,"abstract":"<div><h3>Background and objective</h3><p>Coronavirus Disease 2019 (COVID-19) has been associated with the onset of autoimmune conditions, but whether this relationship is causal remains unknown, partly because robust evidence based on the detection of autoantibodies is lacking. This study explored the potential impact of COVID-19 pandemic on the temporal trends of autoimmunity.</p></div><div><h3>Methods</h3><p>Retrospective analysis of all consecutive autoimmune tests performed at one central laboratory at a University hospital, operating services for 18 other hospitals and clinical laboratories in Belgium, from January 01, 2015 to May 31, 2022. Longitudinal changes in the positivity rates of autoimmunity tests were analyzed, <em>i.e.</em> before and after the onset of the COVID-19 pandemic (March 11, 2020). The tests notably included the detection of autoantibodies associated with type 1 diabetes, thyroid diseases, connective tissue diseases, antiphospholipid syndrome, vasculitis and other organ-specific conditions. Kendall rank correlation test was applied to assess temporal trends.</p></div><div><h3>Results</h3><p>Over a period of 89 months, a total of 301,720 consecutive tests for 24 different autoantibodies among 87,674 unique patients were performed (87% adults, 68% women, mean age 44 ± 20 years). Overall, 52,862 (18%) tests returned positive, with positivity rates for each test ranging between 1% and 46%. No increase in the positivity rate of autoimmunity tests was observed after the start of the pandemic.</p></div><div><h3>Conclusion</h3><p>The onset of the COVID-19 pandemic was not associated with increased positivity rates of a large panel of autoimmune tests. Whether the higher incidence of autoimmune disorders associated with COVID-19 reflects detection bias or reverse causality, or is linked to seronegative autoimmune disorders requires further investigation.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100222"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909023000357/pdfft?md5=69b8ae4c90795eab3d7e3f98ac0994b8&pid=1-s2.0-S2589909023000357-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138475538","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 : 2023-12-01DOI: 10.1016/j.jtauto.2023.100221
Chiara Tani , Chiara Cardelli , Roberto Depascale , Anna Gamba , Luca Iaccarino , Andrea Doria , Matilde Bandeira , Sara Paiva Dinis , Vasco C. Romão , Emanuele Gotelli , Sabrina Paolino , Maurizio Cutolo , Niccolò Di Giosaffatte , Alessandro Ferraris , Paola Grammatico , Lorenzo Cavagna , Veronica Codullo , Carlomaurizio Montecucco , Valentina Longo , Lorenzo Beretta , Marta Mosca
Background
Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety.
Methods
Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points.
Findings
365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period.
Interpretation
COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.
{"title":"Long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases: The ERN-ReCONNET VACCINATE study","authors":"Chiara Tani , Chiara Cardelli , Roberto Depascale , Anna Gamba , Luca Iaccarino , Andrea Doria , Matilde Bandeira , Sara Paiva Dinis , Vasco C. Romão , Emanuele Gotelli , Sabrina Paolino , Maurizio Cutolo , Niccolò Di Giosaffatte , Alessandro Ferraris , Paola Grammatico , Lorenzo Cavagna , Veronica Codullo , Carlomaurizio Montecucco , Valentina Longo , Lorenzo Beretta , Marta Mosca","doi":"10.1016/j.jtauto.2023.100221","DOIUrl":"https://doi.org/10.1016/j.jtauto.2023.100221","url":null,"abstract":"<div><h3>Background</h3><p>Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety.</p></div><div><h3>Methods</h3><p>Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points.</p></div><div><h3>Findings</h3><p>365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period.</p></div><div><h3>Interpretation</h3><p>COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"7 ","pages":"Article 100221"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909023000345/pdfft?md5=c233fe4841cd7c8163b927e103b556f6&pid=1-s2.0-S2589909023000345-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138502001","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}