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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
Impact of imlifidase treatment on immunoglobulins in an HLA-hypersensitized lupus nephritis patient with anti-SSA/SSB antibodies after kidney transplantation: A case report 肾移植后抗 SSA/SSB 抗体的 HLA 超敏狼疮肾炎患者接受亚胺立酶治疗对免疫球蛋白的影响:病例报告
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-12-01 DOI: 10.1016/j.jtauto.2023.100223
Jean Milhès , Olivier Marion , Benedicte Puissant , Caroline Carlé , Charlène Bouthemy , Arnaud Del Bello , Nassim Kamar , Yves Renaudineau , Nicolas Congy-Jolivet

Bacterial recombinant cysteine protease Ides (imlifidase, Idefirix®, Hansa Biopharma) is used to prevent humoral transplant rejection in highly HLA-sensitized recipients, and to control IgG-mediated autoimmune diseases. We report the case of a 51 years old woman suffering from lupus nephritis with end stage kidney disease, grafted for the second time and pre-treated with imlifidase. The patient was HLA-hypersensitized (calculated Panel Reactive Antibodies [Abs], cPRA>99 %) and has three preformed Donor Specific Antibodies (DSA). Circulating immunoglobulins were monitored at initiation (0, 6, 36, 72 and 96 h), and at Ab recovery one and two months following imlifidase injection. From baseline, the higher depletion was reported after 36h for total IgG (−75 %) and IgG subclasses (−87 % for IgG1, IgG2 and IgG3, -78 % for IgG4), while no significant impact on IgA and IgM was observed. Anti-SSA 60 kDa and anti-SSB auto-Abs quickly decreased after imlifidase injection (−96 % for both after 36 h) as well as post-vaccinal specific IgG (−95 % for tetanus toxoid, −97 % for pneumococcus and −91 % for Haemophilus influenzae Abs after 36 h). At the Ab recovery phase, total IgG and anti-SSA60/SSB Abs reached their initial level at two months. Regarding alloreactive Abs, anti-HLA Abs including the three DSA showed a dramatic decrease after injection with 100 % depletion from baseline after 36 h as assessed by multiplex single bead antigen assay, leading to negative crossmatches using both lymphocytotoxicity (LCT) and flow cell techniques. DSA rebound at recovery was absent and remained under the positivity threshold (MFI = 1000) after 6 months. The findings from this case report are that imlifidase exerts an early depleting effect on all circulating IgG, while IgG recovery may depend in part from imlifidase's capacity to target memory B cells.

细菌重组半胱氨酸蛋白酶伊德斯(imlifidase,Idefirix®,Hansa Biopharma)用于预防高度 HLA 敏感受体的体液移植排斥反应,以及控制 IgG 介导的自身免疫性疾病。我们报告了一例患有狼疮性肾炎并伴有终末期肾病的 51 岁女性患者的病例。该患者为 HLA 过敏(计算的反应性抗体[Abs],cPRA>99 %),并有三种预形成的捐献者特异性抗体(DSA)。在开始治疗时(0、6、36、72 和 96 小时)以及注射伊立菲酶后一到两个月的抗体恢复期,对循环免疫球蛋白进行了监测。与基线相比,36 小时后总 IgG(-75%)和 IgG 亚类(IgG1、IgG2 和 IgG3 为-87%,IgG4 为-78%)的消耗较高,而 IgA 和 IgM 则无明显影响。注射伊立菲酶后,抗 SSA 60 kDa 和抗 SSB 自身抗体迅速下降(36 小时后两者均下降了 96%),疫苗接种后特异性 IgG 也迅速下降(36 小时后破伤风类毒素下降了 95%,肺炎球菌下降了 97%,流感嗜血杆菌抗体下降了 91%)。在抗体恢复阶段,总 IgG 和抗 SSA60/SSB 抗体在两个月后达到初始水平。至于同种异体反应性抗体,包括三种 DSA 在内的抗 HLA 抗体在注射后急剧下降,36 小时后从基线 100% 消减,这是由多重单珠抗原检测法评估的,使用淋巴细胞毒性(LCT)和流式细胞技术进行交叉配血均为阴性。恢复时 DSA 没有反弹,6 个月后仍低于阳性阈值(MFI = 1000)。本病例报告的研究结果表明,伊立菲酶对所有循环中的 IgG 均有早期消耗作用,而 IgG 的恢复可能部分取决于伊立菲酶靶向记忆 B 细胞的能力。
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引用次数: 0
Liver inflammation activity in patients with autoimmune hepatitis with normal alanine aminotransferase and immunoglobulin G levels 丙氨酸氨基转移酶和免疫球蛋白 G 水平正常的自身免疫性肝炎患者的肝脏炎症活性
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2023-11-28 DOI: 10.1016/j.jtauto.2023.100220
Yun Chen , Jiacheng Liu , Jian Wang , Weihua Wu , Huali Wang , Yilin Liu , Zhiyi Zhang , Shaoqiu Zhang , Yifan Pan , Yiguang Li , Weimao Ding , Li Zhu , Chuanwu Zhu , Jie Li , Yuanwang Qiu , Rui Huang , Chao Wu

Background and aims

Normal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels.

Methods

Two hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation.

Results

One hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045–1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138–2.014, P = 0.004) were independent factors associated with advanced inflammation.

Conclusions

High proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.

背景和目的血清转氨酶和免疫球蛋白 G (IgG) 水平正常是自身免疫性肝炎(AIH)肝组织学疾病活动性的替代标记物。本研究旨在评估血清丙氨酸氨基转移酶(ALT)和 IgG 水平正常的 AIH 患者的肝脏炎症情况。结果 131 例(63.9%)AIH 患者有晚期肝脏炎症,108 例(52.7%)患者有晚期肝纤维化。60.0%的谷丙转氨酶(ALT)正常患者和51.7%的谷丙转氨酶(ALT)和IgG正常患者患有晚期炎症。然而,在有或没有晚期肝纤维化且 ALT 正常的患者中,76.7% 和 35.0% 有晚期炎症,而在 ALT 和 IgG 正常的患者中,相应的晚期炎症比例分别为 78.6% 和 26.7%。此外,在 ALT 正常的肝硬化患者和非肝硬化患者中,分别有 81.0% 和 44.8% 的人炎症晚期,而在 ALT 和 IgG 正常的患者中,相应比例分别为 83.3% 和 29.4%。红细胞分布宽度(OR = 1.325,95%CI 1.045-1.681,P = 0.020)和 PT(OR = 1.514,95%CI 1.138-2.014,P = 0.004)是与晚期炎症相关的独立因素。尽管使用非侵入性方法有助于排除ALT和IgG水平正常的AIH患者的肝纤维化,但仍鼓励进行肝活检以评估肝脏炎症。
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引用次数: 0
期刊
Journal of Translational Autoimmunity
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