New Insights in the Pathogenesis of Autoimmune Hemolytic Anemia.
New Insights in the Pathogenesis of Autoimmune Hemolytic Anemia.
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自身免疫性溶血性贫血的发病机理的新见解。
DOI：
10.1159/000439002
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发表时间：
2015-09
期刊：
影响因子：
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通讯作者：
Barcellini W
中科院分区：
文献类型：
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作者：
Barcellini W
自身免疫性溶血性贫血（AIHA）是由抗红细胞（RBC）自身抗体在有或没有补体激活的情况下对RBC的破坏增加引起的。RBC破坏可通过补体级联最终组分（膜攻击复合物）的顺序激活直接裂解或通过抗体依赖性细胞介导的细胞毒性（ADCC）发生。自身抗体的致病作用取决于其类别（最常见的是IgG和IgM）、亚类、热振幅（热形式和冷形式）以及激活补体的亲和力和效率。几种细胞因子和细胞毒性机制（CD8+ T和自然杀伤细胞）进一步参与RBC破坏。此外，活化的携带Fc受体的巨噬细胞可以识别并吞噬被自身抗体和补体调理的红细胞。直接补体介导的溶解主要发生在循环和肝脏中，而ADCC、细胞毒性和吞噬作用优先发生在脾脏和淋巴器官中。血管内溶血的程度是血管外溶血的10倍。最后，成红细胞代偿反应的疗效可以极大地影响AIHA的临床表现。所有这些致病机制的相互作用和相对负担为AIHA的巨大临床异质性提供了理由，从完全代偿到迅速演变的致命病例。
Autoimmune hemolytic anemia (AIHA) is caused by the increased destruction of red blood cells (RBCs) by anti-RBC autoantibodies with or without complement activation. RBC destruction may occur both by a direct lysis through the sequential activation of the final components of the complement cascade (membrane attack complex), or by antibody-dependent cell-mediated cytotoxicity (ADCC). The pathogenic role of autoantibodies depends on their class (the most frequent are IgG and IgM), subclass, thermal amplitude (warm and cold forms),as well as affinity and efficiency in activating complement. Several cytokines and cytotoxic mechanisms (CD8+ T and natural killer cells) are further involved in RBC destruction. Moreover, activated macrophages carrying Fc receptors may recognize and phagocyte erythrocytes opsonized by autoantibodies and complement. Direct complement-mediated lysis takes place mainly in the circulations and liver, whereas ADCC, cytotoxicity, and phagocytosis occur preferentially in the spleen and lymphoid organs. The degree of intravascular hemolysis is 10-fold greater than extravascular one. Finally, the efficacy of the erythroblastic compensatory response can greatly influence the clinical picture of AIHA. The interplay and relative burden of all these pathogenic mechanisms give reason for the great clinical heterogeneity of AIHAs, from fully compensated to rapidly evolving fatal cases.