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用于临床转化的类天疱疮疾病模型系统

Pemphigoid disease model systems for clinical translation.

作者信息

Tigges Marvin, Dräger Sören, Piccini Ilaria, Bieber Katja, Vorobyev Artem, Edelkamp Janin, Bertolini Marta, Ludwig Ralf J

机构信息

QIMA Life Sciences, QIMA Monasterium GmbH, Münster, Germany.

Department of Dermatology, University Medical Center of the State of Schleswig-Holstein (UKSH), Lübeck, Germany.

出版信息

Front Immunol. 2025 Mar 17;16:1537428. doi: 10.3389/fimmu.2025.1537428. eCollection 2025.

DOI:10.3389/fimmu.2025.1537428
PMID:40165962
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11955494/
Abstract

Pemphigoid diseases constitute a group of organ-specific autoimmune diseases characterized and caused by autoantibodies targeting autoantigens expressed in the skin and mucous membranes. Current therapeutic options are still based on unspecific immunosuppression that is associated with severe adverse events. Biologics, targeting the IL4-pathway or IgE are expected to change the treatment landscape of pemphigoid diseases. However, clinical studies demonstrated that targeting these pathways alone is most likely not sufficient to meet patient and healthcare partitioners expectations. Hence, model systems are needed to identify and validate novel therapeutic targets in pemphigoid diseases. These include pre-clinical animal models, and model systems, hypothesis-driven drug repurposing, as well as exploitation of real-world-data. In this review, we will highlight the medical need for pemphigoid diseases, and in-depth discuss the advantages and disadvantages of the available pemphigoid disease model systems. Ultimately, we discuss how rapid translation can be achieved for the benefit of the patients.

摘要

类天疱疮疾病是一组器官特异性自身免疫性疾病,其特征是由针对皮肤和黏膜中表达的自身抗原的自身抗体引起。目前的治疗选择仍然基于与严重不良事件相关的非特异性免疫抑制。靶向白细胞介素4通路或免疫球蛋白E的生物制剂有望改变类天疱疮疾病的治疗格局。然而,临床研究表明,仅靶向这些通路很可能不足以满足患者和医疗保健人员的期望。因此,需要模型系统来识别和验证类天疱疮疾病中的新治疗靶点。这些包括临床前动物模型和模型系统、假设驱动的药物再利用,以及对真实世界数据的利用。在这篇综述中,我们将强调类天疱疮疾病的医疗需求,并深入讨论现有类天疱疮疾病模型系统的优缺点。最终,我们将讨论如何实现快速转化以造福患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87a8/11955494/cf5acaf97010/fimmu-16-1537428-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87a8/11955494/5207e25afe19/fimmu-16-1537428-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87a8/11955494/cf5acaf97010/fimmu-16-1537428-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87a8/11955494/5207e25afe19/fimmu-16-1537428-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87a8/11955494/cf5acaf97010/fimmu-16-1537428-g002.jpg

相似文献

1
Pemphigoid disease model systems for clinical translation.用于临床转化的类天疱疮疾病模型系统
Front Immunol. 2025 Mar 17;16:1537428. doi: 10.3389/fimmu.2025.1537428. eCollection 2025.
2
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Severity and phenotype of bullous pemphigoid relate to autoantibody profile against the NH2- and COOH-terminal regions of the BP180 ectodomain.大疱性类天疱疮的严重程度和表型与针对BP180胞外域NH2端和COOH端区域的自身抗体谱相关。
J Invest Dermatol. 2002 Nov;119(5):1065-73. doi: 10.1046/j.1523-1747.2002.19529.x.

本文引用的文献

1
Off-label use of tralokinumab in the treatment of bullous pemphigoid: a case series.曲罗芦单抗在大疱性类天疱疮治疗中的超说明书用药:病例系列
Br J Dermatol. 2025 May 19;192(6):1124-1126. doi: 10.1093/bjd/ljaf035.
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Measurement of the Memory B Cell Response via Antibodies from Activated Cells.通过活化细胞产生的抗体来测量记忆B细胞反应。
Antibodies (Basel). 2024 Oct 3;13(4):81. doi: 10.3390/antib13040081.
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Real-world evaluation of the effectiveness and safety of dupilumab in bullous pemphigoid: an ambispective multicentre case series.
度普利尤单抗治疗大疱性类天疱疮有效性和安全性的真实世界评估:一项前瞻性队列多中心病例系列研究
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A successful experience in treating lichen planus pemphigoides with tofacitinib: a case report.托法替布治疗类天疱疮样扁平苔藓的成功经验:一例报告
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Autoantigen-specific CD4 T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases.自身抗原特异性 CD4 T 细胞获得耗竭表型,并在人类自身免疫性疾病中持续存在。
Immunity. 2024 Oct 8;57(10):2416-2432.e8. doi: 10.1016/j.immuni.2024.08.005. Epub 2024 Sep 2.
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High throughput screening identifies repurposable drugs for modulation of innate and acquired immune responses.高通量筛选鉴定可调节先天和获得性免疫反应的再利用药物。
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Successful treatment of infantile refractory bullous pemphigoid with baricitinib.巴瑞替尼成功治疗小儿难治性大疱性类天疱疮
Australas J Dermatol. 2024 Dec;65(8):642-646. doi: 10.1111/ajd.14345. Epub 2024 Jul 19.
8
Pemphigoid gestationis is associated with an increased risk for adverse pregnancy outcomes: A large-scale propensity-matched retrospective cohort study.妊娠类天疱疮与不良妊娠结局风险增加相关:一项大规模倾向匹配回顾性队列研究。
J Am Acad Dermatol. 2024 Oct;91(4):748-750. doi: 10.1016/j.jaad.2024.05.087. Epub 2024 Jun 19.
9
State-of-the-art diagnosis of autoimmune blistering diseases.自身免疫性水疱病的最新诊断方法。
Front Immunol. 2024 Jun 6;15:1363032. doi: 10.3389/fimmu.2024.1363032. eCollection 2024.
10
Neonatal Fc Receptor Inhibition Reduces Bullous Pemphigoid Anti-Basement Membrane Zone IgG Deposition and Blistering in 3-Dimensional Human Skin Equivalents.新生儿Fc受体抑制可减少大疱性类天疱疮抗基底膜带IgG在三维人皮肤替代物中的沉积及水疱形成。
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