内部炎症动荡:自身炎症性疾病的遗传基础、临床表现和治疗方法探讨。

IF 2 4区 医学 Q3 RHEUMATOLOGY
Kátia Tomie Kozu, Renan Rodrigues Neves Ribeiro do Nascimento, Patrícia Pontes Aires, Rafael Alves Cordeiro, Thais Costa Lima de Moura, Flavio Roberto Sztajnbok, Ivanio Alves Pereira, Adriana Almeida de Jesus, Sandro Félix Perazzio
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引用次数: 0

摘要

全身性自身炎症性疾病(SAIDs)源于先天性免疫系统活动失调,导致全身性炎症。这些疾病包括一系列不同的遗传缺陷,被归类为先天性免疫错误,由于其遗传异质性和临床表现各不相同,因此在诊断上是一个重大挑战。虽然基因测序技术的最新进展促进了致病基因的发现,但仍有约 40% 的 SAIDs 患者缺乏分子诊断。SAIDs 具有不同的临床表型,需要有针对性的治疗方法。本综述旨在强调 SAIDs 的复杂性和临床意义,重点关注根据病理生理学分组的以下典型疾病:(i)炎性体病症,其特点是炎性体过度活化,从而诱发显著的 IL-1β 释放;(ii)继发性病症,这是一种单基因疾病,其特点是 NF-κB 信号通路失调;(iii)IL-18/IL-36 信号通路缺陷诱发的 SAIDs,这是一种自身炎症,其特点是 IL-18/IL-36 细胞因子信号平衡失调,导致炎症失控和组织损伤,主要发生在皮肤;(iv) I 型干扰素病(type I interferonopathies),这是一组以 I 型干扰素(IFNs),特别是干扰素 α、β 和 ε 的失控产生为特征的多种疾病;(v) 抗炎信号通路受损诱发的 SAIDs,这是一组以 IL-10 和 TGFβ 抗炎通路中断为特征的疾病;以及 (vi) 杂项和多基因 SAIDs。后一组包括 VEXAS 综合征、慢性复发性多灶性骨髓炎/慢性非细菌性骨髓炎、Schnitzler 综合征和 Still's 病等,说明 SAID 的异质性和建立全面分类的难度。涉及靶向药物(如 JAK 抑制剂、IL-1 阻断剂和 TNF 抑制剂)的治疗策略是针对特定疾病表型量身定制的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inflammatory turmoil within: an exploration of autoinflammatory disease genetic underpinnings, clinical presentations, and therapeutic approaches.

Systemic autoinflammatory diseases (SAIDs) arise from dysregulated innate immune system activity, which leads to systemic inflammation. These disorders, encompassing a diverse array of genetic defects classified as inborn errors of immunity, are significant diagnostic challenges due to their genetic heterogeneity and varied clinical presentations. Although recent advances in genetic sequencing have facilitated pathogenic gene discovery, approximately 40% of SAIDs patients lack molecular diagnoses. SAIDs have distinct clinical phenotypes, and targeted therapeutic approaches are needed. This review aims to underscore the complexity and clinical significance of SAIDs, focusing on prototypical disorders grouped according to their pathophysiology as follows: (i) inflammasomopathies, characterized by excessive activation of inflammasomes, which induces notable IL-1β release; (ii) relopathies, which are monogenic disorders characterized by dysregulation within the NF-κB signaling pathway; (iii) IL-18/IL-36 signaling pathway defect-induced SAIDs, autoinflammatory conditions defined by a dysregulated balance of IL-18/IL-36 cytokine signaling, leading to uncontrolled inflammation and tissue damage, mainly in the skin; (iv) type I interferonopathies, a diverse group of disorders characterized by uncontrolled production of type I interferons (IFNs), notably interferon α, β, and ε; (v) anti-inflammatory signaling pathway impairment-induced SAIDs, a spectrum of conditions characterized by IL-10 and TGFβ anti-inflammatory pathway disruption; and (vi) miscellaneous and polygenic SAIDs. The latter group includes VEXAS syndrome, chronic recurrent multifocal osteomyelitis/chronic nonbacterial osteomyelitis, Schnitzler syndrome, and Still's disease, among others, illustrating the heterogeneity of SAIDs and the difficulty in creating a comprehensive classification. Therapeutic strategies involving targeted agents, such as JAK inhibitors, IL-1 blockers, and TNF inhibitors, are tailored to the specific disease phenotypes.

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来源期刊
Advances in Rheumatology
Advances in Rheumatology Medicine-Rheumatology
CiteScore
4.00
自引率
4.30%
发文量
41
审稿时长
53 weeks
期刊介绍: Formerly named Revista Brasileira de Reumatologia, the journal is celebrating its 60th year of publication. Advances in Rheumatology is an international, open access journal publishing pre-clinical, translational and clinical studies on all aspects of paediatric and adult rheumatic diseases, including degenerative, inflammatory and autoimmune conditions. The journal is the official publication of the Brazilian Society of Rheumatology and welcomes original research (including systematic reviews and meta-analyses), literature reviews, guidelines and letters arising from published material.
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