Activation of complement system in adult T-cell leukemia (ATL) occurs mainly through lectin pathway: A serum proteomic approach using mass spectrometry
Activation of complement system in adult T-cell leukemia (ATL) occurs mainly through lectin pathway: A serum proteomic approach using mass spectrometry
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DOI：
10.1016/j.canlet.2008.06.004
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发表时间：
2008-11-18
期刊：
影响因子：
9.7
通讯作者：
Okayama, Akihiko
中科院分区：
文献类型：
--
作者：
Ishida, Yo-ichi;Yamashita, Kiyoshi;Okayama, Akihiko
成人 T 细胞白血病 (ATL) 是一种由人类 T 淋巴细胞病毒 1 型 (HTLV-1) 感染引起的致命恶性肿瘤。为了寻找新的 ATL 生物标志物，我们使用 ProteinChip 阵列分析了 ATL 患者的血清。 HTLV-I携带者ATL患者与健康志愿者的光谱比较显示，ATL的5个峰（1779、1866、2022、4467和8930 m/z）的强度显着升高，而4个峰（4067、4151、8130和8597 m/z）的强度降低。从这些差异表达的峰中，我们选择 1779、1866 和 2022 m/z 的峰作为 ATL 的候选生物标志物。使用串联质谱法的 MS/MS 离子搜索和使用抗 C3 抗体的免疫沉淀测定表明，源自这些候选峰的因子被鉴定为 C3f，它是补体系统的组成部分和补体 C3 的片段。这些结果表明补体系统在ATL中被激活。对补体系统中激活途径（经典途径、旁路途径和凝集素途径）特异性标志物的进一步分析表明，ATL患者中凝集素途径标志物的血清浓度明显较高。这些结果表明ATL中补体系统的激活主要通过凝集素途径发生。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
Adult T-cell leukemia (ATL) is a fatal malignancy caused by infection with human T lymphotropic virus type-1 (HTLV-1). To search for a new biomarker of ATL, we analyzed sera from ATL patients using ProteinChip arrays. The spectral comparison of ATL patients with HTLV-I carriers and healthy volunteers showed that the intensities of five peaks (1779, 1866, 2022, 4467, and 8930 m/z) were significantly increased in ATL, while those of four peaks (4067, 4151, 8130, and 8597 m/z) were decreased. From these differentially expressed peaks, we chose peaks of 1779, 1866, and 2022 m/z as biomarker candidates of ATL. MS/MS ion search using tandem mass spectrometry and immunoprecipitation assay using anti-C3 antibody showed that factors derived from these candidate peaks were identified as C3f, which is a component of the complement system and a fragment of complement C3. These results indicate that the complement system was activated in ATL. Further analysis of markers specific to the activation pathways (classical, alternative, and lectin pathways) in the complement system showed that the serum concentration of the marker of the lectin pathway was significantly higher in ATL patients. These results suggest that activation of the complement system in ATL occurs mainly through the lectin pathway. (C) 2008 Elsevier Ireland Ltd. All rights reserved.