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复发性多软骨炎的病因与发病机制

Author
Clement J Michet, MD
Section Editor
Jane Hoyt Buckner, MD
Deputy Editor
Paul L Romain, MD
Translators
朱锦宇, 副主任医师，副教授

引言

复发性多软骨炎(relapsing polychondritis, RPC)是一种全身性炎症性/退行性疾病，其临床表现不一，可能包括：软骨的结构和功能不全；特殊感觉器官受损；以及心血管、肾脏和神经系统受损(表 1)。 (参见“复发性多软骨炎的临床表现”)

本专题将总结我们目前了解到的RPC病因和发病机制。RPC的病理改变将在别处介绍。 (参见“复发性多软骨炎的病理学”)

RPC的诊断和治疗方法参见其他专题。 (参见“复发性多软骨炎的诊断性评估”和“复发性多软骨炎的治疗”)

病因

RPC的病因尚不清楚。尽管只有极少数明确的线索，但RPC似乎具有遗传易感性，与其他免疫异常相关疾病存在相似之处，并可能有多个激发事件(包括化学刺激)。该假设得到了一系列研究结果的支持；它们提示RPC并不是单一疾病，而是与遗传易感个体中多个促发因素相关的综合征。RPC与副肿瘤骨髓异常增生的关系表明，克隆性淋巴样干细胞可能在病理生理学中发挥着作用，其中T细胞功能性缺陷会诱发自身免疫和不受控制的肿瘤性造血干细胞克隆性增殖。然而，一项关于滥用消遣性药物后突发RPC的报告提示，直接的生化刺激也可以诱发本病。 (参见下文‘遗传易感性’和‘与其他免疫性疾病的关联’和‘毒素诱发’)

遗传易感性 — 研究并未发现RPC与人类白细胞抗原(human leukocyte antigen, HLA)Ⅰ类(HLA-A和HLA-B)有关[1]。但据报道，RPC和HLAⅡ类有关，特别是HLA-DR4[2]。研究人员在60例中欧白种RPC患者中对HLAⅡ类组织相容性抗原的出现率进行了遗传分析[2]；结果发现患者的HLA-DR4出现率为56%，而健康对照组的出现率为26%。基因分型结果显示，RPC没有和哪种DR4亚型等位基因存在优先关联，而类风湿关节炎(rheumatoid arthritis, RA)与DRB1*0401和DRB1*0404具有明确关联[3]。这些RA相关的等位基因都有一个序列高度相似的区域，编码共同表位(参见“人类白细胞抗原与其他类风湿关节炎的易感基因”)。此外，研究者在1例RPC患者中发现了一种新的DR4等位基因(DRB1*0421)[4]。因此，尽管RPC和RA可能具有相同的临床和免疫学特征，而且有时候还会同时存在，但HLA-DRB1*04等位基因在这两种疾病中的作用可能不同。

         

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Literature review current through: 2017-06 . | This topic last updated: 2016-11-24.
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