Journal of Translational Autoimmunity最新文献_第5页

A laboratory test to detect gliadin-specific CD4+ T-cells for difficult to diagnose celiac disease 一项检测麦胶蛋白特异性CD4+ t细胞的实验室试验难以诊断乳糜泻

IF 3.6 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-07-24 DOI: 10.1016/j.jtauto.2025.100301

Daan A.R. Castelijn , Nicolette J. Wierdsma , Kim de Buck , Maaike A. van Bree , Tracy-Jane T.H.D. Eisden , Jolien C. Hollander , Gerd Bouma , Hetty J. Bontkes

Objectives

Discrepancy between serology and small bowel histology, such as seronegative CD, poses a diagnostic challenge in celiac disease (CD) diagnosis. Recently described methods to detect gliadin-specific T-cells are too laborious even in a specialized diagnostic setting. We developed a method, which can be implemented in specialized diagnostic laboratories.

Methods

Gliadin-specific T-cells were analyzed by α1-and α2-gliadin peptide loaded Dextramers (Dm) in healthy controls (HC, n = 18), patients with non-celiac gluten sensitivity (NCGS, n = 9), active CD (aCD, n = 7) and CD on a gluten free diet (GFD, n = 14). Control peptide (CLIP)-loaded Dm were used as background controls. The α-gliadin-Dm:CLIP-Dm ratio was calculated. In CD patients ≥5 years on GFD (n = 8), a randomized two-dose gluten challenge was performed to increase gliadin-specific T-cell frequencies.

Results

Gliadin-specific CD4⁺ T-cell frequencies were significantly higher in aCD and GFD than in HC and NCGS (p ≤ 0.0001). In CD patients on a GFD ≥5 years, gliadin-specific T-cells were detectable in 6/8 patients after a week gluten challenge, and all tested positive within 4 weeks. Gliadin-specific T-cells significantly upregulated CD38 after 1 week of gluten ingestion (p < 0.008). Real world data from sixteen patients demonstrated the applicability of this test in diagnostic challenging cases.

Conclusions

Gliadin-specific T-cells can be detected in peripheral blood of CD patients using commercially available dextramers. These cells persist in CD patients on a GFD but may decline over time. A short term low-dose gluten challenge increased sensitivity. This simplified detection method of gliadin-specific T-cells is suitable for diagnostic challenging CD cases.

目的血清学与小肠组织学的差异，如血清乳糜泻阴性，对乳糜泻的诊断提出了挑战。最近描述的检测麦胶蛋白特异性t细胞的方法即使在专门的诊断设置中也过于费力。我们开发了一种方法，可以在专门的诊断实验室实施。方法采用α1和α2麦胶蛋白肽负载葡聚糖（Dm）对健康对照组（HC, n = 18）、非乳糜泻谷蛋白敏感患者（NCGS, n = 9）、活性乳糜泻患者（aCD, n = 7）和无麸质饮食的乳糜泻患者（GFD, n = 14）的麦胶蛋白特异性t细胞进行分析。对照肽（CLIP）加载Dm作为背景对照。计算α-麦胶蛋白- dm:CLIP-Dm比值。在接受GFD治疗≥5年的CD患者中（n = 8），进行随机双剂量谷蛋白刺激以增加麦胶蛋白特异性t细胞频率。结果aCD和GFD的gliadin特异性CD4+ t细胞频率显著高于HC和NCGS （p≤0.0001）。在GFD≥5年的CD患者中，6/8的患者在一周的麸质攻击后检测到麦胶蛋白特异性t细胞，并且在4周内全部检测出阳性。麦胶蛋白特异性t细胞在摄入谷蛋白1周后显著上调CD38 (p <；0.008)。来自16名患者的真实世界数据证明了该测试在诊断挑战性病例中的适用性。结论市售右旋聚物可在CD患者外周血中检测到麦胶蛋白特异性t细胞。这些细胞在患有GFD的乳糜泻患者体内持续存在，但可能随着时间的推移而减少。短期低剂量谷蛋白刺激会增加敏感性。这种简化的麦胶蛋白特异性t细胞检测方法适用于诊断挑战性CD病例。

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引用次数: 0

Matrix remodeling-associated protein 5 as a novel biomarker for predicting disease activity and endoscopic response to infliximab in Crohn's disease 基质重塑相关蛋白5作为预测克罗恩病疾病活动性和内镜下对英夫利昔单抗反应的新生物标志物

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-07-07 DOI: 10.1016/j.jtauto.2025.100300

Daopo Lin , Jiayue Xu , Mengqian Ye , Luyan Fang , Tianhao Xia , Wenyu Tong , Gokuljayanth Jayaseelan Ranichandra , Yifan Bao , Bo Zheng , Yi Jiang , Lianpin Wu , Dingyuan Hu

The primary objective of treating Crohn's disease (CD) is to achieve and sustain endoscopic remission. However, repeated endoscopic examination leads to decreased patient compliance and procedural risks. Non-invasive biomarkers for endoscopic activity of CD are thus promising in clinical use. This study compared proteomic profiles between inflammatory and non-inflammatory intestinal tissues on 10 active CD patients through liquid chromatography–tandem mass spectrometry, and identified 384 differentially expressed proteins. Four candidate secretory proteins (MXRA5, AZU/HBP, CRYAB, DEFA3) were validated via ELISA in serum from 74 CD patients (43 active CD and 31 in remission). Serum MXRA5 levels were notably increased in CD patients in remission compared to active cases (P < 0.001) and showed an inverse correlation with SES-CD scores (r = −0.33, P < 0.05). ROC analysis demonstrated MXRA5's utility in distinguishing endoscopic activity of patients with CD (AUC = 0.80), which was improved when combined with CRP (AUC = 0.89). Besides, higher baseline serum MXRA5 levels predicted better endoscopic response to infliximab (IFX). In conclusion, our study indicates that MXRA5 might serve as a new potential serum biomarker for CD activity and IFX response prediction. Further prospective and muli-center studies are needed to validate its predictive performance.

治疗克罗恩病（CD）的主要目的是实现和维持内窥镜缓解。然而，反复的内镜检查导致患者依从性降低和手术风险。因此，内窥镜下CD活性的非侵入性生物标志物在临床应用中很有前景。本研究通过液相色谱-串联质谱法比较了10例活动性CD患者炎症性和非炎症性肠道组织的蛋白质组学特征，鉴定出384种差异表达蛋白。通过ELISA对74例CD患者（43例活动性CD， 31例缓解期CD）血清中的4种候选分泌蛋白（MXRA5、AZU/HBP、CRYAB、DEFA3）进行了验证。与活动期患者相比，缓解期患者血清MXRA5水平显著升高(P <；0.001)，并与SES-CD评分呈负相关(r = - 0.33, P <；0.05)。ROC分析显示，MXRA5在鉴别CD患者的内镜活动方面具有实用价值（AUC = 0.80），与CRP联合使用（AUC = 0.89）可提高该功能。此外，较高的基线血清MXRA5水平预示着对英夫利昔单抗（IFX）的内镜反应更好。总之，我们的研究表明MXRA5可能作为一种新的潜在的血清生物标志物，用于CD活性和IFX反应预测。需要进一步的前瞻性和多中心研究来验证其预测性能。

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引用次数: 0

Hyperimmunoglobulin syndromes: A review of HIGM, HIES, and HIDS 高免疫球蛋白综合征：HIGM， HIES和HIDS的综述

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-06-27 DOI: 10.1016/j.jtauto.2025.100297

Wushu Chen , Xingpei Li , Junye Mai , Kailang Tang , Yingqiao Wang , Yan-yan Lu , Jie Liang , Ni-jiao Li , Xiu-Yu Qin , Yu Li , Lunkai Yao , Ye Qiu

At present, there is a lack of detailed understanding and research on the pathogenesis and treatment of Hyperimmunoglobulin M syndrome (HIGM), Hyperimmunoglobulin E syndrome (HIES), and hyperimmunoglobulin D syndrome (HIDS), and few studies have been conducted to correlate the pathogenesis and treatment of the three disorders. The existing studies are rarely related to the three diseases. We searched PubMed for a large number of relevant literature and analyzed and summarized the contents. We analyzed and introduced the three diseases and their Categorization, Epidemiology, Clinical manifestations, Laboratory diagnosis, and Treatment by means of tables and Figures. It is hoped that this analysis and summary can play a certain role in the research and treatment of related diseases and promote the understanding and prevention of related diseases.

目前，对高免疫球蛋白M综合征（HIGM）、高免疫球蛋白E综合征（HIES）和高免疫球蛋白D综合征（HIDS）的发病机制和治疗方法缺乏详细的认识和研究，将这三种疾病的发病机制和治疗方法联系起来的研究也很少。现有的研究很少涉及这三种疾病。我们在PubMed检索了大量相关文献，并对内容进行了分析总结。通过图表分析和介绍三种疾病及其分类、流行病学、临床表现、实验室诊断和治疗。希望本文的分析和总结能够对相关疾病的研究和治疗起到一定的作用，促进对相关疾病的认识和预防。

引用次数: 0

Autoimmune manifestations in children with inborn errors of immunity in Morocco: A study from the national registry 摩洛哥先天性免疫缺陷儿童的自身免疫表现：一项来自国家登记处的研究

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-06-26 DOI: 10.1016/j.jtauto.2025.100299

Ahamada Elamine , Ibtihal Benhsaien , Fatima Ailal , Abderrahmane Errami , Zakaria Kasmi , Zahra Aadam , Asmaa Drissi Bourhanbour , Ahmed Aziz Bousfiha , Jalila El Bakkouri

Inborn Errors of Immunity (IEI) are a heterogeneous group of genetic disorders characterized by increased susceptibility to infections and immune dysregulation, including autoimmunity and autoinflammation. Despite their clinical significance, data on autoimmune manifestations in Moroccan pediatric patients with IEI remain limited.

This study aims to investigate the prevalence, spectrum, and clinical patterns of autoimmune manifestations in pediatric patients with IEI in Morocco.

We conducted a retrospective analysis of pediatric patients registered in the Moroccan IEI registry from January 2007 to December 2023. Demographic, clinical, and laboratory data were extracted, with a particular focus on autoimmune manifestations.

Among 769 patients registered in the Moroccan IEI registry, 108 (14 %) exhibited at least one autoimmune manifestation. Consanguinity was observed in 59 (55 %) of cases, and the male-to-female ratio was 1.14. The median age at the onset of clinical symptoms was 10 months (2–33 months), and the median age at IEI diagnosis was 30 months (10.5–84 months). A total of 191 autoimmune manifestations were recorded among these patients, with a notable predominance of autoimmune cytopenia (72 %), followed by cutaneous (10 %) and gastrointestinal (9 %) manifestations. Poly-autoimmunity was present in 47.3 % of affected patients. The most frequently associated IEI subtype with these autoimmune manifestations was common variable immunodeficiency (16,7 %).

Autoimmune manifestations are a frequent complication in Moroccan children with IEI, with autoimmune cytopenias predominating. A high index of suspicion for IEI should be maintained in patients initially presenting with autoimmunity, particularly autoimmune cytopenia. These patients require personalized management due to their higher risk of mortality.

先天性免疫错误（IEI）是一组异质性遗传疾病，其特征是对感染和免疫失调的易感性增加，包括自身免疫和自身炎症。尽管具有临床意义，但摩洛哥儿童IEI患者自身免疫表现的数据仍然有限。本研究旨在调查摩洛哥IEI患儿自身免疫表现的患病率、频谱和临床模式。我们对2007年1月至2023年12月在摩洛哥IEI登记处登记的儿科患者进行了回顾性分析。提取了人口统计学、临床和实验室数据，特别关注自身免疫表现。在摩洛哥IEI登记处登记的769例患者中，108例（14%）表现出至少一种自身免疫表现。有血缘关系59例（55%），男女比例为1.14。出现临床症状时的中位年龄为10个月（2-33个月），IEI诊断时的中位年龄为30个月（10.5-84个月）。这些患者共记录了191种自身免疫性表现，其中以自身免疫性细胞减少症为主（72%），其次是皮肤（10%）和胃肠道（9%）表现。47.3%的患者存在多重自身免疫。与这些自身免疫表现最常相关的IEI亚型是常见的可变免疫缺陷（16.7%）。自身免疫表现是摩洛哥IEI患儿的常见并发症，以自身免疫细胞减少症为主。对于最初表现为自身免疫，特别是自身免疫性细胞减少症的患者，应保持对IEI的高度怀疑。这些患者由于死亡风险较高，需要个性化治疗。

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引用次数: 0

An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacy 一项国际多中心回顾性分析，在ana相关的风湿病中反复进行抗ena检测，一项数据驱动的建议，以提高检测效果

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-06-25 DOI: 10.1016/j.jtauto.2025.100298

Wim H.M. Vroemen , Maria Infantino , Mariangela Manfredi , Joyce J.B.C. van Beers , Carolien Bonroy , Jan G.M.C. Damoiseaux

Background

Autoantibodies detection in ANA-associated rheumatic diseases (AARD) is not only used for diagnostic and classification purposes, but also for monitoring. In case of AARD it is questioned if repeated anti-ENA testing is of any substantial value. In this international multicenter retrospective study, repeated anti-ENA testing according to local AARD testing algorithms was investigated.

Methods

Anti-ENA results (anti-SSA60, -Ro52, -SSB, -Scl-70, -CENP-B, -RNP, -Sm) over a 6 to 10-year period were extracted from the laboratory information systems of three participating centers. Time between repeated testing was determined and concordance analysis was performed.

Results

The study included 28557 anti-ENA requests from 19388 patients (72 % female). In 15227 patients (78.5 %) only one anti-ENA test was performed (79.9 % negative), while 4161 patients (21.5 %) underwent multiple (median [interquartile range (IQR)]; 2 [2–4]) tests with a maximum of 31 tests. The median [IQR] time interval between anti-ENA testing for the total cohort was 364 [195–539] days. Concordance analysis demonstrated that repeated anti-ENA test results did not show any change in 3583 patients (86.1 %). Additional autoantibodies were observed in 243 patients (5.8 %). In 76 (1.8 %) patients a positive anti-ENA test was obtained after an initial negative anti-ENA test result, while in 167 (4.0 %) patients additional autoantibodies were detected after an initial positive anti-ENA result.

Conclusions

Repeated anti-ENA testing with a median time interval of about one year is common independently of local laboratory testing algorithms, but showed a limited added value since only 1.8 % of the patients have demonstrated a positive anti-ENA test after an initial negative anti-ENA test. These data at least suggest that repeated anti-ENA tests should be discouraged and only be instigated by a change in clinical manifestations.

自身抗体检测在ana相关性风湿病（AARD）中不仅用于诊断和分类，而且用于监测。在AARD的情况下，反复的抗ena测试是否有任何实质性的价值是值得怀疑的。在这项国际多中心回顾性研究中，研究了根据局部AARD检测算法进行的重复抗ena检测。方法从三个参与中心的实验室信息系统中提取6 ~ 10年间的抗- ena结果（抗- ssa60、-Ro52、-SSB、-Scl-70、-CENP-B、-RNP、-Sm）。确定重复试验的间隔时间并进行一致性分析。结果该研究包括19388例患者的28557份抗ena申请（72%为女性）。在15227例（78.5%）患者中，仅进行了一次抗ena检测（79.9%为阴性），而4161例（21.5%）患者进行了多次(中位数[四分位数范围（IQR）]；2[2 - 4])个测试例，最多31个测试例。在整个队列中，抗ena检测的中位数[IQR]时间间隔为364[195-539]天。一致性分析表明，3583例（86.1%）患者的重复抗ena检测结果未显示任何变化。243例（5.8%）患者检测到自身抗体。在76例（1.8%）患者中，在最初的抗ena测试结果为阴性后，检测到抗ena阳性，而在167例（4.0%）患者中，在最初的抗ena阳性结果后检测到额外的自身抗体。结论：在独立于当地实验室检测算法的情况下，以中位时间间隔约一年进行重复的抗ena检测是很常见的，但其附加价值有限，因为在最初的抗ena检测阴性后，只有1.8%的患者显示出抗ena检测阳性。这些数据至少表明，应该不鼓励重复的抗ena试验，只有在临床表现发生变化时才应该进行。

{"title":"An international multicenter retrospective analysis of repeated anti-ENA testing in ANA-associated rheumatic diseases, a data-driven proposal to increase testing efficacy","authors":"Wim H.M. Vroemen , Maria Infantino , Mariangela Manfredi , Joyce J.B.C. van Beers , Carolien Bonroy , Jan G.M.C. Damoiseaux","doi":"10.1016/j.jtauto.2025.100298","DOIUrl":"10.1016/j.jtauto.2025.100298","url":null,"abstract":"<div><h3>Background</h3><div>Autoantibodies detection in ANA-associated rheumatic diseases (AARD) is not only used for diagnostic and classification purposes, but also for monitoring. In case of AARD it is questioned if repeated anti-ENA testing is of any substantial value. In this international multicenter retrospective study, repeated anti-ENA testing according to local AARD testing algorithms was investigated.</div></div><div><h3>Methods</h3><div>Anti-ENA results (anti-SSA60, -Ro52, -SSB, -Scl-70, -CENP-B, -RNP, -Sm) over a 6 to 10-year period were extracted from the laboratory information systems of three participating centers. Time between repeated testing was determined and concordance analysis was performed.</div></div><div><h3>Results</h3><div>The study included 28557 anti-ENA requests from 19388 patients (72 % female). In 15227 patients (78.5 %) only one anti-ENA test was performed (79.9 % negative), while 4161 patients (21.5 %) underwent multiple (median [interquartile range (IQR)]; 2 [2–4]) tests with a maximum of 31 tests. The median [IQR] time interval between anti-ENA testing for the total cohort was 364 [195–539] days. Concordance analysis demonstrated that repeated anti-ENA test results did not show any change in 3583 patients (86.1 %). Additional autoantibodies were observed in 243 patients (5.8 %). In 76 (1.8 %) patients a positive anti-ENA test was obtained after an initial negative anti-ENA test result, while in 167 (4.0 %) patients additional autoantibodies were detected after an initial positive anti-ENA result.</div></div><div><h3>Conclusions</h3><div>Repeated anti-ENA testing with a median time interval of about one year is common independently of local laboratory testing algorithms, but showed a limited added value since only 1.8 % of the patients have demonstrated a positive anti-ENA test after an initial negative anti-ENA test. These data at least suggest that repeated anti-ENA tests should be discouraged and only be instigated by a change in clinical manifestations.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100298"},"PeriodicalIF":4.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dysregulation of innate and adaptive lymphoid immunity may have implications for symptom attribution and predict responses to targeted therapies in neuropsychiatric systemic lupus erythematosus 先天性和适应性淋巴细胞免疫失调可能与神经精神系统性红斑狼疮的症状归因有关，并预测对靶向治疗的反应

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-06-11 DOI: 10.1016/j.jtauto.2025.100296

Julius Lindblom , Guillermo Barturen , Lorenzo Beretta , Daniel Toro-Domínguez , Elena Carnero-Montoro , Maria Orietta Borghi , Jessica Castillo , Ellen Iacobaeus , Yvonne Enman

Objectives

To gain insights into the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) and identify potential drug targets through investigation of whole-blood human transcriptome.

Methods

We analysed differentially expressed genes in peripheral blood from active central nervous system (CNS) lupus (n = 26) and active non-neuropsychiatric SLE (n = 38) patients versus healthy controls (n = 497) from the European PRECISESADS project (NTC02890121). We further explored dysregulated gene modules in active CNS lupus and their correlation with serological markers. Lastly, we performed regulatory network and druggability analysis.

Results

Unsupervised weighted gene co-expression network analysis (WGCNA) revealed 23 dysregulated gene modules and two subgroups of active CNS lupus. The interferon gene module was prominently upregulated in subgroup 1, while the B cell, T cell, and cytotoxic/natural killer (NK) cell modules were downregulated. Subgroup 2 showed less marked dysregulation patterns. Subgroup 1 had lower estimated proportions of lymphoid cell subsets and proportionally more patients positive for anti-dsDNA antibodies compared to subgroup 2, pointing to molecularly distinct subgroups or misclassification of subgroup 2. In silico prediction algorithms demonstrated a greater anticipated response to anifrolumab, C3 inhibitors, and calcineurin inhibitors for patients in CNS lupus subgroup 1 compared with subgroup 2.

Conclusions

Gene dysregulation patterns related to innate and adaptive lymphoid immunity separated active CNS lupus patients into two distinct subgroups with differential anticipated response to type I interferon, C3, and calcineurin inhibition. Our study provides a conceptual framework for precision medicine in NPSLE and implications for overcoming the major clinical challenge of attributing neuropsychiatric features to SLE versus other causes.

目的通过对人全血转录组的研究，了解神经精神系统性红斑狼疮（NPSLE）的发病机制，并寻找潜在的药物靶点。方法我们分析了来自欧洲PRECISESADS项目（NTC02890121）的活动性中枢神经系统（CNS）狼疮（n = 26）和活动性非神经精神性SLE （n = 38）患者与健康对照组（n = 497）外周血中差异表达的基因。我们进一步探讨了活动性中枢神经系统狼疮中失调的基因模块及其与血清学标志物的相关性。最后，我们进行了监管网络和药物分析。结果监督加权基因共表达网络分析（WGCNA）揭示了23个基因模块和两个中枢神经系统狼疮亚群。干扰素基因模块在亚组1中显著上调，而B细胞、T细胞和细胞毒性/自然杀伤（NK）细胞模块下调。亚组2表现出较不明显的失调模式。与亚组2相比，亚组1淋巴样细胞亚群的估计比例更低，抗dsdna抗体阳性的患者比例更多，这表明亚组2分子不同或分类错误。计算机预测算法显示，与2亚组相比，CNS狼疮1亚组患者对anfrolumab、C3抑制剂和钙调磷酸酶抑制剂的预期反应更大。结论先天性和适应性淋巴细胞免疫相关的基因失调模式将活动性中枢神经系统狼疮患者分为两个不同的亚组，对I型干扰素、C3和钙调磷酸酶抑制的预期反应不同。我们的研究为NPSLE的精准医学提供了一个概念框架，并为克服将神经精神特征归因于SLE与其他原因的主要临床挑战提供了启示。

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引用次数: 0

The ‘autoimmunome’ of centenarians 百岁老人的“自身免疫组”

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-06-07 DOI: 10.1016/j.jtauto.2025.100295

Pedro Carrera-Bastos , Abel Plaza-Florido , Alejandro Santos-Lozano , Vânia Borba , Gabriel Rodríguez-Romo , Celia García-Chico , Simone Lista , Gonzalo Saco-Ledo , Enzo Emanuele , Yehuda Shoenfeld , Alejandro Lucia

Objective

To identify signature proteins potentially linked to resistance to autoimmunity in the blood of centenarians.

Methods

We conducted in silico data mining of previously published proteomic results using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and PHENOPEDIA databases.

Results

Sixteen autoimmune disease-related proteins were identified within the proteomic signatures of centenarians. Albumin was the most connected hub protein, notably elevated in centenarians compared to younger controls, suggesting a protective role. Eight of the identified autoimmunity-related proteins—ADIPOQ, C1S, C5, C7, C9, CFD, MASP1, and SERPING1—were associated with the complement system.

Conclusion

Elevated albumin levels and a prominent complement system presence in centenarians' blood proteome may contribute to resistance to autoimmunity, highlighting potential protective mechanisms against autoimmune diseases in extreme longevity.

目的鉴定百岁老人血液中可能与自身免疫抵抗相关的特征蛋白。方法利用Search Tool for Retrieval of Interacting Genes/Proteins （STRING）和PHENOPEDIA数据库对已发表的蛋白质组学结果进行计算机数据挖掘。结果在百岁老人的蛋白质组学特征中鉴定出16种自身免疫性疾病相关蛋白。白蛋白是最相关的中心蛋白，与年轻的对照组相比，百岁老人的白蛋白明显升高，这表明白蛋白具有保护作用。鉴定出的8种自身免疫相关蛋白（adipoq、C1S、C5、C7、C9、CFD、MASP1和serping1）与补体系统相关。结论百岁老人血液蛋白质组中白蛋白水平的升高和补体系统的显著存在可能有助于自身免疫的抵抗，揭示了超长寿命对自身免疫性疾病的潜在保护机制。

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引用次数: 0

A comparative study of different assays for autoantibodies detection in patients with autoimmune gastritis 不同方法检测自身免疫性胃炎患者自身抗体的比较研究

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-05-24 DOI: 10.1016/j.jtauto.2025.100294

Małgorzata Osmola , Caroline Hémont , Marcin Romańczyk , Amaury Druet , Nicolas Chapelle , Tamara Matysiak-Budnik , Marco Vincenzo Lenti , Jérôme C. Martin

Objective

Autoimmune gastritis (AIG) is an important health problem and a risk factor for gastric neoplasms. This study assessed the diagnostic performance of different assays for anti-parietal cell antibodies (APCA) and anti-intrinsic factor antibodies (AIFA) in patients with histologically confirmed AIG.

Methods

This prospective, multicenter study included 50 AIG patients and 93 controls. The diagnostic performance of fluorescent enzyme immunoassay (FEIA) and immunoblot was evaluated for the detection of both APCA and AIFA, while indirect immunofluorescence (IIF) was assessed for APCA only.

Results

Overall, AIFA detection using FEIA demonstrated slightly better performance (specificity [Sp] 100 %, positive predictive value [PPV] 100 %, negative predictive value [NPV] 75 %) compared to immunoblot (Sp 98.9 %, PPV 94.1 %, NPV 73 %). However, both methods showed low sensitivity (Se): 38 % for FEIA and 32 % for immunoblot. When the FEIA cut-off was adjusted using ROC curve analysis, Se increased to 50 %, while maintaining high Sp (98.9 %). For APCA detection, Se was similar across all methods (∼80 %), but Sp varied: immunoblot showed lower Sp (89.3 %) compared to IIF (98.8 %) and FEIA (95.7 %). PPV was highest for IIF (97.5 %), followed by FEIA (89.9 %) and immunoblot (89.3 %). NPV was lowest for immunoblot (80 %), while IIF and FEIA showed comparable values (89.5 % and 90.9 %, respectively). Adjusting the FEIA cut-off for APCA increased Sp to 98.9 % without reducing Se (76 %). Combining AIFA and APCA testing improved diagnostic performance, yielding a sensitivity of 90 % and specificity of 95.7 %.

Conclusions

FEIA offers superior diagnostic accuracy for APCA and AIFA testing in AIG. The highest diagnostic yield for AIG is observed when both APCA and AIFA are assessed. This approach could be clinically applicable in the screening for AIG and diagnostic process of AIG.

目的自身免疫性胃炎（AIG）是重要的健康问题，也是胃肿瘤发生的危险因素之一。本研究评估了抗壁细胞抗体（APCA）和抗内因子抗体（AIFA）的不同检测方法对组织学证实的AIG患者的诊断效果。方法本前瞻性、多中心研究纳入50例AIG患者和93例对照组。采用荧光酶免疫分析法（FEIA）和免疫印迹法（immunoblot）检测APCA和AIFA，采用间接免疫荧光法（indirect immunofluorescence， IIF）检测APCA。结果总体而言，FEIA检测AIFA的特异性[Sp] 100%，阳性预测值[PPV] 100%，阴性预测值[NPV] 75%，优于免疫印迹（Sp 98.9%, PPV 94.1%, NPV 73%）。然而，两种方法都显示出低灵敏度（Se）： FEIA为38%，免疫印迹为32%。当使用ROC曲线分析调整FEIA截止时，Se增加到50%，同时保持较高的Sp（98.9%）。对于APCA检测，所有方法的Se相似（~ 80%），但Sp不同：免疫印迹显示Sp（89.3%）低于IIF（98.8%）和FEIA（95.7%）。IIF的PPV最高（97.5%），其次是FEIA（89.9%）和免疫印迹（89.3%）。免疫印迹的NPV最低（80%），而IIF和FEIA的NPV值相当（分别为89.5%和90.9%）。调整FEIA的APCA截止值将Sp增加到98.9%，而不降低Se（76%）。结合AIFA和APCA检测提高了诊断性能，敏感性为90%，特异性为95.7%。结论feia对AIG的APCA和AIFA检测具有较高的诊断准确性。当同时评估APCA和AIFA时，观察到AIG的最高诊断率。该方法在临床上可用于AIG的筛查和诊断过程。

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引用次数: 0

Epigenetic regulation of thrombo-inflammation in Behçet and antiphospholipid syndrome behet和抗磷脂综合征中血栓炎症的表观遗传调控

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-05-24 DOI: 10.1016/j.jtauto.2025.100293

Alessandra Bettiol , Giacomo Bagni , Francesca Di Patti , Elena Lastraioli , Alice Barinotti , Massimo Radin , Savino Sciascia , Domenico Prisco , Annarosa Arcangeli , Giacomo Emmi

Background

An epigenetic regulation of thrombo-inflammation has been reported in Behçet syndrome (BS), likely driven by a unique profile of three plasmatic circulating microRNAs (ci-miRNAs) (miR-206, miR-224-5p, and miR-653-5p). We compared this ci-miRNAs expression in BS and antiphospholipid syndrome (APS), the prototype of acquired pro-thrombotic autoimmune disease. To further corroborate the hypothesis that shared mechanisms drive the thrombotic process in BS and APS, we further assessed their thrombin generation assay (TGA) profile.

Methods

The three ci-miRNA expression was evaluated in 39 patients with BS, 33 with APS and 30 healthy controls (HCs). Single marker and combined ROC curve analyses were performed. TGA was conducted on pre-collected platelet poor plasma samples from 35 patients with BS and 77 with APS.

Results

The three ci-miRNAs, taken individually or combined, lacked acceptable discriminating power between groups [AUC from combiROC 0.64 (95 % CI: 0.51–0.78)]. Conversely, in the subgroups of BS and APS patients with vascular involvement (n = 22 each), the combined signature well discriminated between the two syndromes [AUC 0.83 (0.71–0.96), specificity 0.91, sensitivity 0.77], as well as between thrombotic APS and HCs [AUC 0.79 (0.64–0.91)]. Also, distinct trends in thrombograms emerged between BS and APS, with BS TGA displaying lower tLag and tPeak, higher Peak and similar AUC as compared to APS.

Conclusions

Despite shared elements in the ci-miRNA regulation of their pro-thrombotic tendency, distinct epigenetic factors seem to contribute to the pathogenesis of vascular events in BS and APS, possibly accounting also for the different global clotting assay observed in these diseases.

behet综合征（BS）的血栓炎症的表观遗传调控已被报道，可能是由三种血浆循环microrna （ci- mirna）的独特谱（miR-206， miR-224-5p和miR-653-5p）驱动的。我们比较了这种ci-miRNAs在BS和抗磷脂综合征（APS）中的表达，APS是获得性促血栓性自身免疫性疾病的原型。为了进一步证实BS和APS的共同机制驱动血栓形成过程的假设，我们进一步评估了它们的凝血酶生成测定（TGA）谱。方法对39例BS患者、33例APS患者和30例健康对照（hc）进行3种ci-miRNA的表达测定。进行单标记和联合ROC曲线分析。对35例BS患者和77例APS患者预采集的血小板不良血浆样本进行TGA分析。结果这3种CI - mirna，单独或联合使用，在组间缺乏可接受的鉴别能力[组合roc的AUC为0.64 (95% CI: 0.51-0.78)]。相反，在血管受损伤的BS和APS患者亚组（n = 22）中，两种综合征（AUC 0.83(0.71-0.96)，特异性0.91，敏感性0.77）以及血栓性APS和hcc之间的联合特征（AUC 0.79(0.64-0.91)）得到了很好的区分。此外，BS和APS之间的血栓图呈现出明显的趋势，与APS相比，BS TGA显示出较低的flag和tPeak，较高的Peak和相似的AUC。结论：尽管ci-miRNA调控其促血栓倾向的共同因素，但不同的表观遗传因素似乎有助于BS和APS血管事件的发病机制，可能也解释了在这些疾病中观察到的不同的整体凝血测定。

{"title":"Epigenetic regulation of thrombo-inflammation in Behçet and antiphospholipid syndrome","authors":"Alessandra Bettiol , Giacomo Bagni , Francesca Di Patti , Elena Lastraioli , Alice Barinotti , Massimo Radin , Savino Sciascia , Domenico Prisco , Annarosa Arcangeli , Giacomo Emmi","doi":"10.1016/j.jtauto.2025.100293","DOIUrl":"10.1016/j.jtauto.2025.100293","url":null,"abstract":"<div><h3>Background</h3><div>An epigenetic regulation of thrombo-inflammation has been reported in Behçet syndrome (BS), likely driven by a unique profile of three plasmatic circulating microRNAs (ci-miRNAs) (miR-206, miR-224-5p, and miR-653-5p). We compared this ci-miRNAs expression in BS and antiphospholipid syndrome (APS), the prototype of acquired pro-thrombotic autoimmune disease. To further corroborate the hypothesis that shared mechanisms drive the thrombotic process in BS and APS, we further assessed their thrombin generation assay (TGA) profile.</div></div><div><h3>Methods</h3><div>The three ci-miRNA expression was evaluated in 39 patients with BS, 33 with APS and 30 healthy controls (HCs). Single marker and combined ROC curve analyses were performed. TGA was conducted on pre-collected platelet poor plasma samples from 35 patients with BS and 77 with APS.</div></div><div><h3>Results</h3><div>The three ci-miRNAs, taken individually or combined, lacked acceptable discriminating power between groups [AUC from combiROC 0.64 (95 % CI: 0.51–0.78)]. Conversely, in the subgroups of BS and APS patients with vascular involvement (n = 22 each), the combined signature well discriminated between the two syndromes [AUC 0.83 (0.71–0.96), specificity 0.91, sensitivity 0.77], as well as between thrombotic APS and HCs [AUC 0.79 (0.64–0.91)]. Also, distinct trends in thrombograms emerged between BS and APS, with BS TGA displaying lower tLag and tPeak, higher Peak and similar AUC as compared to APS.</div></div><div><h3>Conclusions</h3><div>Despite shared elements in the ci-miRNA regulation of their pro-thrombotic tendency, distinct epigenetic factors seem to contribute to the pathogenesis of vascular events in BS and APS, possibly accounting also for the different global clotting assay observed in these diseases.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100293"},"PeriodicalIF":4.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characteristics of polyclonal anti-interferon-gamma autoantibodies and novel diagnostic strategies: A prospective cohort study of new biomarkers 多克隆抗干扰素γ自身抗体的特征和新的诊断策略：一项新的生物标志物的前瞻性队列研究

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-05-15 DOI: 10.1016/j.jtauto.2025.100292

Xidong Wang , Feng Ye , Hongling Liu , Shaoqiang Li , Jinglu Yang , Xue Yu , Yilei Hui , Yongming Li , Yangqing Zhan , Yan Wang , Jing Liu , Zhengtu Li

Background

Anti-γ interferon autoantibody (AIGA) syndrome is a widespread and grossly underestimated immunodeficiency disorder characterized by high mortality rates and a lack of standardized diagnostic methods. A highly accurate AIGA biomarker that meets the requirements of absolute quantification is urgently needed to enable the early diagnosis and treatment monitoring of the disease. In our study, we aimed to identify the primary components of AIGAs, determine their function, and develop a novel diagnostic method.

Methods

Immune repertoire sequencing and a retrospective antibody subtype index analysis were performed for typical patients. Affinity chromatography was used to isolate and purify IgGs from AIGAs in the plasma of AIGA(+) patients. The clinical application value of chromatography for testing AIGAs was evaluated in a prospective clinical cohort.

Results

A total of 114 eligible subjects were enrolled. Immune repertoire sequencing revealed that 74 % of the AIGA(+) patients had IgG clone types, with the somatic hypermutation (SHM) analysis being the most informative. We isolated AIGAs from the blood and interpreted their affinity and major components completely. Based on the results of this prospective cohort study, AIGAs, an absolute quantitative biomarker, were significantly better than the ELISA method (Delong test, P = 0.0018).

Conclusions

Patients with AIGA syndrome have abnormally elevated IgG levels, with IgG3 subtypes dominating. The disorder is characterized by the rapid acquisition of polyclonal AIGAs. The obtained AIGAs had a good neutralization capacity and potential as absolute quantitative biomarkers.

抗γ干扰素自身抗体（AIGA）综合征是一种广泛存在且被严重低估的免疫缺陷疾病，其特点是高死亡率和缺乏标准化的诊断方法。迫切需要一种高精度、满足绝对定量要求的AIGA生物标志物，实现疾病的早期诊断和治疗监测。在我们的研究中，我们旨在鉴定aiga的主要成分，确定其功能，并开发一种新的诊断方法。方法对典型患者进行免疫库测序和回顾性抗体亚型指数分析。采用亲和层析法分离纯化AIGA（+）患者血浆中的IgGs。在前瞻性临床队列中评估色谱法检测aiga的临床应用价值。结果共纳入114名符合条件的受试者。免疫库测序显示，74%的AIGA（+）患者具有IgG克隆类型，其中体细胞超突变（SHM）分析是最具信息量的。我们从血液中分离出AIGAs，并完全解释了它们的亲和力和主要成分。本前瞻性队列研究结果显示，绝对定量生物标志物AIGAs明显优于ELISA法（Delong检验，P = 0.0018）。结论AIGA综合征患者IgG水平异常升高，且以IgG3亚型为主。该疾病的特点是快速获得多克隆AIGAs。获得的AIGAs具有良好的中和能力，具有作为绝对定量生物标志物的潜力。

{"title":"Characteristics of polyclonal anti-interferon-gamma autoantibodies and novel diagnostic strategies: A prospective cohort study of new biomarkers","authors":"Xidong Wang , Feng Ye , Hongling Liu , Shaoqiang Li , Jinglu Yang , Xue Yu , Yilei Hui , Yongming Li , Yangqing Zhan , Yan Wang , Jing Liu , Zhengtu Li","doi":"10.1016/j.jtauto.2025.100292","DOIUrl":"10.1016/j.jtauto.2025.100292","url":null,"abstract":"<div><h3>Background</h3><div><em>Anti</em>-γ interferon autoantibody (AIGA) syndrome is a widespread and grossly underestimated immunodeficiency disorder characterized by high mortality rates and a lack of standardized diagnostic methods. A highly accurate AIGA biomarker that meets the requirements of absolute quantification is urgently needed to enable the early diagnosis and treatment monitoring of the disease. In our study, we aimed to identify the primary components of AIGAs, determine their function, and develop a novel diagnostic method.</div></div><div><h3>Methods</h3><div>Immune repertoire sequencing and a retrospective antibody subtype index analysis were performed for typical patients. Affinity chromatography was used to isolate and purify IgGs from AIGAs in the plasma of AIGA(+) patients. The clinical application value of chromatography for testing AIGAs was evaluated in a prospective clinical cohort.</div></div><div><h3>Results</h3><div>A total of 114 eligible subjects were enrolled. Immune repertoire sequencing revealed that 74 % of the AIGA(+) patients had IgG clone types, with the somatic hypermutation (SHM) analysis being the most informative. We isolated AIGAs from the blood and interpreted their affinity and major components completely. Based on the results of this prospective cohort study, AIGAs, an absolute quantitative biomarker, were significantly better than the ELISA method (Delong test, P = 0.0018).</div></div><div><h3>Conclusions</h3><div>Patients with AIGA syndrome have abnormally elevated IgG levels, with IgG3 subtypes dominating. The disorder is characterized by the rapid acquisition of polyclonal AIGAs. The obtained AIGAs had a good neutralization capacity and potential as absolute quantitative biomarkers.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100292"},"PeriodicalIF":4.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0