Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies
Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies
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DOI：
10.1002/cncr.20477
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发表时间：
2004-09-01
期刊：
影响因子：
6.2
通讯作者：
Keating, M
中科院分区：
文献类型：
--
作者：
Albitar, M;Do, KA;Keating, M
背景。 CD52 抗原是一种锚定在成熟 B 和 T 淋巴细胞、单核细胞和嗜酸性粒细胞细胞膜上的糖蛋白。阿仑单抗（CAM-PATH-1H；抗 CD52）目前被批准用于治疗难治性慢性淋巴细胞白血病 (CLL) 患者。作者研究了 CD52 从细胞中脱落的可能性，一旦溶解，可能与注射的阿仑单抗结合，形成免疫复合物。方法。作者使用蛋白质印迹分析、免疫沉淀和酶联免疫吸附测定来研究 117 名 CLL 患者血浆样本中可溶性 CD52 (sCD52) 的存在。他们还使用体外混合实验来检查 sCD52 与细胞竞争和隔离治疗性阿仑单抗的能力。结果。作者在 CLL 患者的血浆样本中检测到高水平的 sCD52。 sCD52 可以在体外与细胞竞争与阿仑单抗的结合，并且可以在接受阿仑单抗的患者体内形成复合物。发现血浆 sCD52 水平与 Rai 分期 (P = 0.0001)、β-2-微球蛋白 (β-2M) 水平 (P = 0.00002)、可溶性 CD23 水平 (r = 0.42，P < 0.001) 和免疫球蛋白突变状态 (P = 0.003) 相关。在针对 β-2M 水平进行调整的多变量分析中，sCD52 水平 > 2336 nM/L 的患者死亡风险增加了近 4 倍。当 sCD52 水平较低时，血浆阿仑单抗水平较高。结论。这些数据不仅证明了 sCD52 在 CLL 患者的分期和监测中是可检测的和有用的，而且还表明 sCD52 与阿仑单抗形成免疫复合物，并可能影响阿仑单抗治疗的疗效和毒性。 (C) 2004 年美国癌症协会。
BACKGROUND. The CD52 antigen is a glycoprotein anchored on the cell membrane of mature B and T lymphocytes, monocytes, and eosinophils. Alemtuzumab (CAM-PATH-1H; anti-CD52) is currently approved for the treatment of patients with refractory chronic lymphocytic leukemia (CLL). The authors investigated the possibility that CD52 may be shed from cells and, once soluble, may bind to injected alemtuzumab, forming immune complexes.METHODS. The authors used Western blot analysis, immunoprecipitation, and enzyme-linked immunoadsorbent assay to investigate the presence of soluble CD52 (sCD52) in the plasma specimens of 117 patients with CLL. They also used in vitro mixing experiments to examine the ability of sCD52 to compete with cells and sequester therapeutic alemtuzumab.RESULTS. The authors detected high levels of sCD52 in the plasma specimens of patients with CLL. sCD52 can compete with cells in vitro for binding to alemtuzumab, and can form complexes in patients receiving alemtuzumab. Plasma levels of sCD52 were found to be correlated (r)with Rai stage (P = 0.0001), beta-2-microglobulin (beta-2M) levels (P = 0.00002), soluble CD23 levels (r = 0.42, P < 0.001), and immunoglobulin mutation status (P = 0.003). In the multivariate analysis adjusted for beta-2M level, patients with sCD52 levels > 2336 nM/L had a nearly 4-fold increase in risk of death. Higher levels of plasma alemtuzumab were achieved when levels of sCD52 were lower.CONCLUSIONS. These data not only demonstrated that sCD52 was detectable and useful in the staging and monitoring of patients with CLL, but also showed that sCD52 formed immune complexes with alemtuzumab and may influence the efficacy and toxicity of alemtuzumab therapy. (C) 2004 American Cancer Society.