PDF(Pubmed)
Abstract：
Relapsing polychondritis is a chronic autoimmune inflammatory condition characterized by recurrent episodes of inflammation at the level of cartilaginous structures and tissues rich in proteoglycans. The pathogenesis of the disease is complex and still incompletely elucidated. The data support the important role of a particular genetic predisposition, with HLA-DR4 being considered an allele that confers a major risk of disease occurrence. Environmental factors, mechanical, chemical or infectious, act as triggers in the development of clinical manifestations, causing the degradation of proteins and the release of cryptic cartilage antigens. Both humoral and cellular immunity play essential roles in the occurrence and perpetuation of autoimmunity and inflammation. Autoantibodies anti-type II, IX and XI collagens, anti-matrilin-1 and anti-COMPs (cartilage oligomeric matrix proteins) have been highlighted in increased titers, being correlated with disease activity and considered prognostic factors. Innate immunity cells, neutrophils, monocytes, macrophages, natural killer lymphocytes and eosinophils have been found in the perichondrium and cartilage, together with activated antigen-presenting cells, C3 deposits and immunoglobulins. Also, T cells play a decisive role in the pathogenesis of the disease, with relapsing polychondritis being considered a TH1-mediated condition. Thus, increased secretions of interferon γ, interleukin (IL)-12 and IL-2 have been highlighted. The \"inflammatory storm\" formed by a complex network of pro-inflammatory cytokines and chemokines actively modulates the recruitment and infiltration of various cells, with cartilage being a source of antigens. Along with RP, VEXAS syndrome, another systemic autoimmune disease with genetic determinism, has an etiopathogenesis that is still incompletely known, and it involves the activation of the innate immune system through different pathways and the appearance of the cytokine storm. The clinical manifestations of VEXAS syndrome include an inflammatory phenotype often similar to that of RP, which raises diagnostic problems. The management of RP and VEXAS syndrome includes common immunosuppressive therapies whose main goal is to control systemic inflammatory manifestations. The objective of this paper is to detail the main etiopathogenetic mechanisms of a rare disease, summarizing the latest data and presenting the distinct features of these mechanisms.
摘要：
复发性多软骨炎是一种慢性自身免疫性炎症性疾病，其特征是在软骨结构和富含蛋白聚糖的组织水平上反复发作的炎症。该疾病的发病机制是复杂的，仍未完全阐明。数据支持特定遗传易感性的重要作用，HLA-DR4被认为是赋予疾病发生主要风险的等位基因。环境因素,机械,化学或传染性，作为临床表现发展的触发因素，导致蛋白质的降解和隐匿性软骨抗原的释放。体液免疫和细胞免疫在自身免疫和炎症的发生和延续中起着至关重要的作用。抗II型自身抗体,IX和XI胶原蛋白，抗苦参素-1和抗COMPs（软骨寡聚基质蛋白）的滴度增加，与疾病活动相关，并考虑预后因素。先天性免疫细胞，中性粒细胞，单核细胞,巨噬细胞，在软骨膜和软骨中发现了自然杀伤淋巴细胞和嗜酸性粒细胞，连同活化的抗原呈递细胞，C3沉积物和免疫球蛋白。此外，T细胞在疾病的发病机制中起着决定性的作用，复发性多软骨炎被认为是TH1介导的疾病。因此，干扰素γ的分泌增加，白细胞介素（IL）-12和IL-2已被强调。由促炎细胞因子和趋化因子组成的复杂网络形成的“炎症风暴”积极调节各种细胞的募集和浸润，软骨是抗原的来源。随着RP,VEXAS综合征,另一种具有遗传决定论的全身性自身免疫性疾病，其病因尚不完全清楚，它涉及通过不同途径激活先天免疫系统和细胞因子风暴的出现。VEXAS综合征的临床表现包括通常与RP相似的炎症表型，这引发了诊断问题。RP和VEXAS综合征的治疗包括常见的免疫抑制疗法，其主要目标是控制全身炎症表现。本文的目的是详细介绍一种罕见疾病的主要病因机制，总结最新数据并介绍这些机制的独特特征。
