Autoantibodies frequently detected in patients with aplastic anemia
Autoantibodies frequently detected in patients with aplastic anemia
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DOI：
10.1182/blood-2002-11-3409
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发表时间：
2003-12-15
期刊：
影响因子：
20.3
通讯作者：
Nadler, LM
中科院分区：
文献类型：
--
作者：
Hirano, N;Butler, MO;Nadler, LM
尽管越来越多的证据强烈表明再生障碍性贫血 (AA) 是一种 T 细胞介导的自身免疫性疾病，但尚未描述 AA 的靶抗原。在自身免疫性疾病中，目标自身抗原不仅经常诱导细胞 T 细胞反应，而且还诱导体液 B 细胞反应。我们假设抗原特异性自身抗体的存在可以用作鉴定 AA 患者中目标 T 细胞自身抗原的“替代标记”。我们筛选了人类胎儿肝脏文库针对造血干/祖细胞抗原的血清学反应性，并分离了 32 个基因。在 18 名 AA 患者中，有 7 名检测到对其中一种基因激动素的免疫球蛋白 G (IgG) 抗体反应，该基因在所有测试的造血细胞谱系中表达，包括 CD34(+) 细胞。在健康志愿者、多次输血的非 AA 患者或患有其他自身免疫性疾病的患者中未检测到对激肽的反应。针对 Kinectin 的 IgG 自身抗体的表位作图显示，不同 AA 患者对几个表位的反应是相同的。此外，针对kinectin衍生肽的CD8(+)细胞毒性T细胞以HLA I类限制的方式抑制粒细胞巨噬细胞集落形成单位(CFU-GM)的集落形成。这些结果表明，kinectin 可能是参与 AA 病理生理学的候选自身抗原。 (C) 2003 年，美国血液学会。
Although accumulating evidence strongly suggests that aplastic anemia (AA) is a T cell-mediated autoimmune disease, no target antigens have yet been described for AA. In autoimmune diseases, target autoantigens frequently induce not only cellular T-cell responses but also humoral B-cell responses. We hypothesized that the presence of antigen-specific autoantibodies could be used as a "surrogate marker" for the identification of target T-cell autoantigens in AA patients. We screened a human fetal liver library for serologic reactivity against hematopoietic stem/progenitor cell antigens and isolated 32 genes. In 7 of 18 AA patients, an immunoglobulin G (IgG) antibody response was detected to one of the genes, kinectin, which is expressed in all hematopoietic cell lineages tested including CD34(+) cells. No response to kinectin was detected in healthy volunteers, multiply transfused non-AA patients, or patients with other autoimmune diseases. Epitope mapping of IgG autoantibodies against kinectin revealed that the responses to several of the epitopes were shared by different AA patients. Moreover, CD8(+) cytotoxic T cells raised against kinectin-derived peptides suppressed the colony formation of granulocyte macrophage colony-forming units (CFU-GMs) in an HLA class I-restricted fashion. These results suggest that kinectin may be a candidate autoantigen that is involved in the pathophysiology of AA. (C) 2003 by The American Society of Hematology.