Fagiolo E, Toriani-Terenzi C
Laboratory of Immunohematology, Catholic University of Sacro Cuore, Rome, Italy.
Autoimmunity. 2003 Jun;36(4):199-204. doi: 10.1080/0891693031000151238.
Recent studies on animal and human autoimmune hemolytic anemia (AIHA) suggest that immunological tolerance loss toward red blood cells (RBC) self-antigens may be originate by different, non-mutually exclusive, mechanisms. According to now available data the identified mechanisms may be: ignorance against RBC self-antigens; molecular mimicry; polyclonal T and/or B cells activation; errors in central or peripheral tolerance; immunoregulatory disorders including cytokine network alteration. In some patients with AIHA, stimulation of PMBC by synthetic Rh peptides indicate that ignorant T and/or B cell clones may recognize cryptic RBC self-antigens. AIHA associated with bacterial or viral infections seems to be produced by polyclonal T and/or B cells activation against foreign antigens which mimic protein or carbohydrate epitopes on RBC. Polyclonal activation of host B cell clones by donor alloreactive T cells causes the AIHA in chronic GVHD. As the tolerance loss is concerned, experiments on mouse lines expressing a transgene with autoantibody activity against murine RBC have shown that non-deleted peripheral B cell clones may produce RBC autoantibodies. In humans a genetic defect of Fas/FasL autoreactive lymphocytes apoptosis may be associated to AIHA. Immunoregulatory disorders due to depletion of CD4+ CD25+ T cells or Th1/Th2 cytokines imbalance may induce autoimmune diseases. In mice AIHA may be induced or improved by cytokines or anticytokine antibodies administration. In NZB/W mice and human AIHA there is an increased production of Th2 cytokines as IL4 and IL10 but INF-gamma reduced production. In addition in human AIHA has been shown a downregulation of IL12 and therefore, an IL10/IL12 immunoregulatory circuit imbalance which might facilitate the RBC autoantibodies production.
近期对动物和人类自身免疫性溶血性贫血（AIHA）的研究表明，针对红细胞（RBC）自身抗原的免疫耐受丧失可能源于不同的、并非相互排斥的机制。根据目前可得的数据，已确定的机制可能有：对RBC自身抗原的忽视；分子模拟；多克隆T和/或B细胞激活；中枢或外周耐受中的错误；免疫调节紊乱，包括细胞因子网络改变。在一些AIHA患者中，合成Rh肽对外周血单核细胞（PMBC）的刺激表明，被忽视的T和/或B细胞克隆可能识别隐蔽的RBC自身抗原。与细菌或病毒感染相关的AIHA似乎是由针对模仿RBC上蛋白质或碳水化合物表位的外来抗原的多克隆T和/或B细胞激活所引起。供体同种异体反应性T细胞对宿主B细胞克隆的多克隆激活导致慢性移植物抗宿主病（GVHD）中的AIHA。就耐受丧失而言，对表达具有针对鼠RBC自身抗体活性转基因的小鼠品系进行的实验表明，未被清除的外周B细胞克隆可能产生RBC自身抗体。在人类中，Fas/FasL自身反应性淋巴细胞凋亡的遗传缺陷可能与AIHA相关。由于CD4 + CD25 + T细胞耗竭或Th1/Th2细胞因子失衡导致的免疫调节紊乱可能诱发自身免疫性疾病。在小鼠中，给予细胞因子或抗细胞因子抗体可诱发或改善AIHA。在NZB/W小鼠和人类AIHA中，Th2细胞因子如IL4和IL10的产生增加，但INF-γ的产生减少。此外，在人类AIHA中已显示IL12下调，因此，IL10/IL12免疫调节回路失衡可能促进RBC自身抗体的产生。
