Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies
Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies
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DOI：
10.1007/s10875-008-9187-2
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发表时间：
2008-05-01
影响因子：
9.1
通讯作者：
Kiss, Maria Helena
中科院分区：
文献类型：
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作者：
Carneiro-Sampaio, Magda;Liphaus, Bernadete Lourdes;Kiss, Maria Helena
简介 对系统性红斑狼疮 (SLE) 和原发性免疫缺陷 (PID) 之间的关联进行分析，以深入了解 SLE 的病理生理学。一些 PID 一直与 SLE 或狼疮样表现相关：(a) 经典补体途径早期成分的纯合性缺陷，按以下降序排列：在 C1q 中，93% 的受影响患者发展为 SLE； C4中，75%；在 C1r/s 中，57%；在C2中，高达25%； (b) X连锁慢性肉芽肿病等位基因的女性携带者； (c) IgA 缺乏，约 5% 的青少年 SLE 存在。讨论 在前两组中，细胞废物处理紊乱被认为是发病机制的主要机制。另一方面，非常有趣的是，PID与几种尚未描述的SLE自身免疫表现系统相关，例如自身免疫性多内分泌病念珠菌病外胚层营养不良（APECED）、免疫调节性多内分泌病X连锁肠病（IPEX）和自身免疫性淋巴增殖综合征（ALPS），这表明被认为是诱导和维持耐受性的关键机制。自身抗原，例如（1）AME介导的淋巴细胞胸腺阴性选择，（2）Foxp3+调节性T细胞介导的外周耐受，以及（3）Fas介导的细胞凋亡删除自身反应性淋巴细胞，与SLE病理生理学无关。无丙种球蛋白血症患者中对 SLE 的未描述和最具特征性的 SLE 临床特征也是有趣的观察结果，这强化了 B 淋巴细胞和抗体在 SLE 发病机制中的重要作用。结论因此，单基因 PID 代表了独特且尚未完全探索的人类模型，用于解开以 SLE（一种典型的多基因疾病）的病理生理学为代表的难题的组成部分。
Introduction Associations between systemic lupus erythematosus (SLE) and primary immunodeficiencies (PIDs) were analyzed to gain insight into the physiopathology of SLE. Some PIDs have been consistently associated with SLE or lupus-like manifestations: (a) homozygous deficiencies of the early components of the classical complement pathway in the following decreasing order: in C1q, 93% of affected patients developed SLE; in C4, 75%; in C1r/s, 57%; and in C2, up to 25%; (b) female carriers of X-linked chronic granulomatous disease allele; and (c) IgA deficiency, present in around 5% of juvenile SLE.Discussion In the first two groups, disturbances of cellular waste-disposal have been proposed as the main mechanisms of pathogenesis. On the other hand and very interestingly, there are PIDs systematically associated with several autoimmune manifestations in which SLE has not been described, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), immunedys-regulation polyendocrinopathy enteropathy X-linked (IPEX), and autoinumme lymphoproliferative syndrome (ALPS), suggesting that mechanisms considered as critical players for induction and maintenance of tolerance to autoantigens, such as (1) AME-mediated thymic negative selection of lymphocytes, (2) Foxp3+ regulatory T cell-mediated peripheral tolerance, and (3) deletion of auto-reactive lymphocytes by Fas-mediated apoptosis, could not be relevant in SLE physiopathology. The non-description of SLE and neither the most characteristic SLE clinical features among patients with agammaglobulinemia are also interesting observations, which reinforce the essential role of B lymphocytes and antibodies for SLE pathogenesis.Conclusion Therefore, monogenic PIDs represent unique and not fully explored human models for unraveling components of the conundrum represented by the physiopathology of SLE, a prototypical polygenic disease.