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恶性肿瘤相关再生障碍性贫血样综合征和再生障碍性贫血患者中抗碳酸酐酶 I IgG 识别的表位重叠。

Overlap of epitopes recognized by anti-carbonic anhydrase I IgG in patients with malignancy-related aplastic anemia-like syndrome and in patients with aplastic anemia.

机构信息

Department of Biological and Biochemical Sciences, University of Pardubice, Pardubice, Czech Republic.

出版信息

Immunol Lett. 2013 Jun;153(1-2):47-9. doi: 10.1016/j.imlet.2013.07.006. Epub 2013 Jul 26.

DOI:10.1016/j.imlet.2013.07.006
PMID:23892086
Abstract

High titers of anti-carbonic anhydrase I (anti-CA I) autoantibodies were detected in the sera of patients with malignancies who developed an aplastic anemia-like (AA-like) syndrome after a high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). It was found, that the presence of these anti-CA I autoantibodies is associated with spontaneous tumor regression. The main immunodominant epitopes of carbonic anhydrase isoform I (CA I) have previously been identified using epitope extraction technique in combination with mass spectrometric detection and bioinformatic verification. Similarly, the sera of patients with bona fide aplastic anemia (AA) who poorly responded to immunosuppressive treatment with anti-thymocyte globulin (ATG) demonstrated high titers of anti-CA I antibodies. In order to reveal differences between these antibodies, we applied the same methodology of epitope mapping procedure. Surprisingly, the anti-CA I antibodies from the both groups of patients compatibly recognized the same four candidate CA I epitopes--DGLAV, NVGHS, SLKPI, SSEQL. This finding may indicate common pathophysiological mechanisms in these two syndromes. However, at this moment it remains unresolved if anti-CA I antibodies are implicated in marrow or tumor suppression or are just an epi-phenomenon.

摘要

在接受大剂量化疗(HDT)和自体干细胞移植(ASCT)后发生再生障碍性贫血样(AA 样)综合征的恶性肿瘤患者的血清中,检测到高滴度的抗碳酸酐酶 I(anti-CA I)自身抗体。研究发现,这些抗 CA I 自身抗体的存在与自发肿瘤消退有关。先前已经使用表位提取技术结合质谱检测和生物信息学验证,鉴定了碳酸酐酶同工酶 I(CA I)的主要免疫优势表位。同样,对免疫抑制治疗抗胸腺细胞球蛋白(ATG)反应不佳的真性再生障碍性贫血(AA)患者的血清也显示出高滴度的抗 CA I 抗体。为了揭示这些抗体之间的差异,我们应用了相同的表位作图程序方法。令人惊讶的是,来自两组患者的抗 CA I 抗体可兼容地识别相同的四个候选 CA I 表位-DGLAV、NVGHS、SLKPI、SSEQL。这一发现可能表明这两种综合征存在共同的病理生理机制。然而,目前仍不清楚抗 CA I 抗体是否参与骨髓或肿瘤抑制,或者仅仅是一种表型现象。

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