Albitar Maher, Do Kim-Anh, Johnson Marcella M, Giles Francis J, Jilani Iman, O'Brien Susan, Cortes Jorge, Thomas Deborah, Rassenti Laura Z, Kipps Thomas J, Kantarjian Hagop M, Keating Michael
Department of Hematopathology, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92690-6130, USA.
Cancer. 2004 Sep 1;101(5):999-1008. doi: 10.1002/cncr.20477.
The CD52 antigen is a glycoprotein anchored on the cell membrane of mature B and T lymphocytes, monocytes, and eosinophils. Alemtuzumab (CAMPATH-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.
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.
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.
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.
CD52抗原是一种糖蛋白，锚定在成熟B淋巴细胞、T淋巴细胞、单核细胞和嗜酸性粒细胞的细胞膜上。阿仑单抗（CAMPATH-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可能从细胞上脱落的可能性，并且一旦可溶，可能会与注射的阿仑单抗结合，形成免疫复合物。
作者使用蛋白质印迹分析、免疫沉淀和酶联免疫吸附测定法，研究117例CLL患者血浆标本中可溶性CD52（sCD52）的存在情况。他们还进行了体外混合实验，以检测sCD52与细胞竞争并隔离治疗性阿仑单抗的能力。
作者在CLL患者的血浆标本中检测到高水平的sCD52。sCD52在体外可与细胞竞争结合阿仑单抗，并可在接受阿仑单抗治疗的患者体内形成复合物。发现sCD52的血浆水平与Rai分期（r）相关（P = 0.0001）、β2微球蛋白（β2M）水平（P = 0.00002）、可溶性CD23水平（r = 0.42，P < 0.001）以及免疫球蛋白突变状态（P = 0.003）。在针对β2M水平进行校正的多变量分析中，sCD52水平> 2336 nM/L的患者死亡风险增加近4倍。当sCD52水平较低时，可达到更高水平的血浆阿仑单抗。
这些数据不仅证明sCD52在CLL患者的分期和监测中可检测且有用，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。
