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Association of CCR6 functional polymorphisms with Primary Biliary Cholangitis CCR6 功能多态性与原发性胆汁性胆管炎的关系
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2024-02-15 DOI: 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.

原发性胆汁性胆管炎患者的胆道上皮细胞会释放CC趋化因子受体6(CCR6)配体20(CCL20),导致CCR6+T细胞招募并随后浸润胆道上皮细胞。先前的全基因组多国荟萃分析(包括我们的汉族队列)显示,CCR6 和 CCL20 单核苷酸多态性(SNP)与原发性胆汁性胆管炎有显著相关性。我们在此报告,根据我们的中国汉族全基因组关联研究,在 CCR6 位点上发现的明显相关 SNP 可分为 "保护 "组和 "风险 "组,但只有 "风险 "SNP 通过单独的中国汉族 PBC 队列得到证实。在汉族 PBC 队列中仅观察到 CCL20 SNPs 的弱关联。精细图谱绘制和逻辑分析确定了一个先前定义的功能变异,该变异导致 CCR6 表达增加,从而增加了汉族队列中 PBC 的遗传易感性。
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引用次数: 0
Evaluating the inhibition of IL-17A and TNFα in a cartilage explant model cultured with Th17-derived cytokines 在使用 Th17 衍生细胞因子培养的软骨外植体模型中评估 IL-17A 和 TNFα 的抑制作用
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2024-01-07 DOI: 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
导言T-17(Th17)辅助细胞产生的 IL-17A 在激活导致关节组织炎症和破坏的致病链中发挥着关键作用。在银屑病关节炎(PsA)和强直性脊柱炎(AS)患者的皮损、血液和滑液中检测到 Th17 细胞和 IL-17A 水平升高。此外,IL-17A 抑制剂可抑制银屑病、银屑病关节炎和强直性脊柱炎的疾病活动,支持 IL-17A 在疾病发病机制中发挥作用的证据。尽管IL-17A抑制剂已被广泛批准,但目前仍不清楚IL-17A的抑制作用如何改变Th17条件下炎症环境中关节的细胞外基质(ECM)。因此,本研究旨在建立一个用 Th17 细胞和抑制剂的条件培养基培养的软骨模型,以探讨 IL-17A 抑制对关节组织重塑的影响。方法将健康人水包衣中的幼稚 CD4+ T 细胞分化成 Th17 细胞,然后激活 Th17 细胞,使其向培养基中分泌 Th17 相关细胞因子和分子。从条件培养基(CM)中分离出活化的 Th17 细胞,并使用流式细胞术进行分析,以验证 Th17 细胞的分化。用酶联免疫吸附法(ELISA)对条件培养基进行评估,以量化 Th17 细胞分泌到培养基中的细胞因子浓度。用 Th17-CM 培养健康牛软骨外植体,并用 IL-17A 和 TNFα 抑制剂处理 21 天。在软骨培养物收获的上清液中,通过 ELISA 测量 MMP 和 ADAMTS 介导的 II 型胶原、凝集素和纤连蛋白的生物标志物片段,以研究软骨组织内的 ECM 重塑情况。II 型胶原和凝集素降解的标志物上调,而 II 型胶原形成的合成代谢标志物与未处理的外植体保持相似水平。在 Th17-CM 中添加 IL-17A 抑制剂可降低升高的 II 型胶原和凝集素降解,但与未处理组相比,退化水平仍然升高。与未经处理的外植体相比,TNFα抑制剂可完全减少II型胶原和骨凝胶的降解。此外,与未处理组相比,TNFα 抑制剂处理并没有改变 II 型胶原的形成。结论本研究表明,在 Th17 调理的软骨组织中抑制 IL-17A 只部分减少了 MMP 介导的 II 型胶原降解和 ADAMTS 介导的骨凝集素降解,而 TNFα 抑制剂处理则完全减少了 MMP 和 ADAMTS 介导的 ECM 降解。这项探索性研究将 ECM 生物标志物与 Th17 调节的体外模型相结合,在描述关节疾病机制和预测治疗对关节组织结构的影响方面具有很大的潜力。
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引用次数: 0
Thymoma with immunodeficiency, combined diffuse panbronchiolitis, and latent autoimmune diabetes in adults- case report and systematic review 胸腺瘤伴有免疫缺陷、合并弥漫性泛细支气管炎和潜伏性自身免疫性糖尿病的成人--病例报告和系统综述
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-12-24 DOI: 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.

胸腺瘤伴免疫缺陷综合征(Good's Syndrome,GS)是胸腺瘤与免疫缺陷之间的一种罕见关联,60 多年前首次被描述。GS患者通常表现为胸腺瘤、外周血中B细胞减少或缺失、低丙种球蛋白血症和细胞介导的免疫缺陷。我们报告了一例 67 岁女性患者的病例,她在出现进行性、严重、难治性肺部感染和弥漫性泛细支气管炎(DPB)后被诊断为 GS。她还患有以抗谷氨酸脱羧酶抗体阳性为特征的糖尿病,因此被诊断为成人潜伏性自身免疫性糖尿病(LADA)。对现有文献的深入研究表明,胸腺瘤术后多次发生机会性感染或自身免疫性疾病后,通常会确诊为 GS。由于免疫缺陷,GS 患者经常会长期反复感染,有些患者会因严重感染而死亡。定期输注免疫球蛋白可有效治疗 GS。
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引用次数: 0
ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization ANKRD22 会加重败血症诱导的 ARDS 并促进肺 M1 巨噬细胞极化
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-12-21 DOI: 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.

急性呼吸窘迫综合征(ARDS)与败血症患者的不良预后密切相关。巨噬细胞 M1 极化在这一过程中起着重要作用。因此,探索影响急性肺损伤和巨噬细胞 M1 极化的关键分子可能为治疗脓毒症 ARDS 提供治疗靶点。在这里,我们通过分析高通量数据发现,脓毒症患者体内含Ankyrin重复结构域蛋白22(ANKRD22)水平的升高与不良预后和更明显的巨噬细胞M1极化有关。在脓毒症 ARDS 模型小鼠的肺泡灌洗液、外周血和肺组织中,ANKRD22 的表达也明显上调。敲除ANKRD22能显著减轻脓毒症诱导的ARDS小鼠的急性肺损伤,并减少肺巨噬细胞的M1极化。此外,在巨噬细胞中删除ANKRD22可抑制巨噬细胞的M1极化,降低磷酸化IRF3的水平和细胞内干扰素调节因子3(IRF3)的表达,而重新表达ANKRD22可逆转这些变化。进一步的实验发现,ANKRD22通过与线粒体抗病毒信号蛋白(MAVS)结合来促进IRF3的激活。总之,这些研究结果表明,ANKRD22能促进肺巨噬细胞的M1极化,并加剧败血症诱发的ARDS。
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引用次数: 0
Novel insights into the complex interplay of immune dysregulation and inflammatory biomarkers in preeclampsia and fetal growth restriction: A two-step Mendelian randomization analysis 子痫前期和胎儿生长受限中免疫失调和炎症生物标志物复杂相互作用的新见解:两步孟德尔随机分析法
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-12-21 DOI: 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。
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引用次数: 0
Ulcerative colitis with autoimmune thyroid disease results in bilateral auricular ossificans:a case 溃疡性结肠炎合并自身免疫性甲状腺疾病导致双侧耳廓骨化:一例
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-12-20 DOI: 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.

背景溃疡性结肠炎(UC)患者通常易患多种自身免疫性疾病,如斯尤格林综合征、原发性硬化性胆管炎、系统性红斑狼疮和胰岛素依赖型糖尿病。这种倾向可能源于免疫介导疾病的共同致病机制。本报告强调了自身免疫性甲状腺疾病在 UC 恶化期间的发生。病例摘要:一名 57 岁的男性主诉持续腹痛、腹泻、便血和粘液,病程长达 20 天。通过结肠镜检查、组织病理学检查和小肠 MRE,确诊为 UC。临床评估显示,他的双耳异位骨化,似乎是在不明时间段内形成的。影像学和组织学评估证实了异位骨化的诊断,同时排除了肾上腺功能不全的可能性。本病例是一个独特的双侧耳骨化病例,据推测可能是甲状腺功能亢进所致。医务工作者应认识到自身免疫性甲状腺疾病在 UC 患者中的潜在重叠性。无论是否存在明显的甲状腺功能障碍,都必须对此类患者进行甲状腺相关抗体检测。
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引用次数: 0
Effect of traditional therapeutics on prevalence and clinical outcomes of coronavirus disease 2019 in Chinese patients with autoimmune diseases 传统疗法对 2019 年中国自身免疫性疾病患者冠状病毒病发病率和临床结果的影响
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-12-12 DOI: 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.

2019冠状病毒病(COVID-19)大流行对自身免疫性疾病(AID)患者的影响一直是一个重要的焦点。本研究旨在分析COVID-19感染艾滋病患者的发病率、临床表现和住院情况,并分析免疫调节药物与这些结果的关系。从2023年1月1日至2月28日,通过在线调查工具和打印件评估aids合并COVID-19感染患者的临床、人口学、维持治疗、症状和病程数据以及结果。共有432名艾滋病患者参加了这项研究。结果显示,羟基氯喹(HCQ)是最常见的常规合成疾病缓解抗风湿药物。使用csDMARDs不会增加COVID-19感染的风险。需要住院治疗的患者明显年龄较大。ILD与较高的住院率相关。除钙调磷酸酶抑制剂(CNI)外,没有其他csdmard与住院风险增加相关。摄入HCQ与咳嗽有关。与无糖皮质激素(GCs)组相比,高剂量GCs组胃肠道症状和心动过速比例较高,喉咙痛和衰老比例较低。GCs并未引起AID患者的COVID - 19感染,但在需要住院治疗的患者中,慢性口服GCs更为常见,且GCs剂量越大,住院风险越高。97名患者在感染后停用csDMARDs,导致住院风险升高。同时,与维持组相比,停用csDMARDs与更高的疾病爆发几率和更低的缓解比例相关。总的来说,我们的分析提供的证据表明,在COVID-19大流行期间,对艾滋病患者进行csdmard的维持治疗可能更为谨慎。
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引用次数: 0
The autoimmune tautology revisited 自身免疫重言论
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-12-01 DOI: 10.1016/j.jtauto.2023.100204
Juan-Manuel Anaya, Santiago Beltrán
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引用次数: 0
Impact of the COVID-19 pandemic on temporal trends of biological indicators of autoimmunity COVID-19大流行对自身免疫生物学指标时间趋势的影响
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-12-01 DOI: 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.

背景和目的2019冠状病毒病(COVID-19)与自身免疫性疾病的发病有关,但这种关系是否存在因果关系尚不清楚,部分原因是缺乏基于自身抗体检测的有力证据。本研究探讨了COVID-19大流行对自身免疫时间趋势的潜在影响。方法回顾性分析2015年1月1日至2022年5月31日在比利时某大学医院的一个中心实验室、其他18家医院和临床实验室进行的所有连续自身免疫检测。分析了自身免疫检测阳性率的纵向变化,即在2019冠状病毒病大流行(2020年3月11日)发生前后。这些检测主要包括检测与1型糖尿病、甲状腺疾病、结缔组织疾病、抗磷脂综合征、血管炎和其他器官特异性疾病相关的自身抗体。采用肯德尔秩相关检验评估时间趋势。结果在89个月的时间里,共对87,674例独特患者(87%为成人,68%为女性,平均年龄44±20岁)进行了24种不同自身抗体的301,720次连续检测。总体而言,52,862例(18%)检测结果呈阳性,每次检测的阳性率在1%至46%之间。大流行开始后,自身免疫试验的阳性率未见增加。结论:COVID-19大流行的发生与大量自身免疫检测的阳性率升高无关。与COVID-19相关的自身免疫性疾病的较高发病率是否反映了检测偏差或反向因果关系,或者是否与血清阴性自身免疫性疾病有关,还需要进一步调查。
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引用次数: 0
Long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases: The ERN-ReCONNET VACCINATE study 罕见和复杂结缔组织疾病患者接种COVID-19疫苗的长期结局:ERN-ReCONNET疫苗接种研究
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-12-01 DOI: 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.

疫苗接种是控制COVID-19大流行的最重要措施之一,特别是对体弱患者。VACCINATE是由欧洲罕见和复杂结缔组织和肌肉骨骼疾病参考网络(ERN ReCONNET)推动的一项多中心前瞻性观察性研究,旨在评估罕见和复杂结缔组织疾病(rcCTDs)患者接种COVID-19疫苗的长期疗效和安全性。方法入选成人rcctd患者。在入组时收集人口统计、临床和疫苗接种数据。在第一个疫苗接种周期完成后的第4、12、24、36和48周安排随访;在这些时间点收集了有关不良事件、疾病恶化和新发SARS-CoV-2感染的数据。结果:共纳入365例rcCTDs患者(87%为女性,平均年龄51.8±14.6岁)。总体而言,200名患者(54.8%)经历了至少一次不良事件,通常是轻微的,在大多数情况下发生在接种疫苗后的早期。在随访期间,39名患者(10.7%)记录了55次疾病恶化,分布在整个观察期,尽管最常见的是在疫苗接种周期完成后的4周内。新发SARS-CoV-2感染的发生率为每1000人月8.9例,接种疫苗后12周内无病例发生,感染脱离初次接种周期呈上升趋势。在研究期间,仅报告了一例严重的COVID-19病例。covid -19疫苗接种在rcctd患者中似乎是有效和安全的。新发感染率相当低,严重感染在我们的队列中并不常见。与既往病史相比,未观察到疾病发作风险增加;然而,这种恶化可能是潜在的严重,强调需要密切监测我们的患者。
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引用次数: 0
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Journal of Translational Autoimmunity
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