Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumab
Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumab
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DOI：
10.1182/blood-2007-09-112052
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发表时间：
2008-04-01
期刊：
影响因子：
20.3
通讯作者：
Papayannopoulou, Thalia
中科院分区：
文献类型：
--
作者：
Bonig, Halvard;Wundes, Annette;Papayannopoulou, Thalia
阻断CD49d介导的淋巴细胞交易已被用于治疗某些自身免疫性疾病，如多发性硬化症(MS)。除了对成熟淋巴细胞向炎症部位的运输产生负面影响外，在小鼠和猴子中阻断CD49d还能迅速动员能够短期和长期植入的造血干细胞/祖细胞(HSPC)。在此，我们的目的是确定抗CD49d抗体在人类(接受CD49d封闭抗体Natalizumab输注的MS患者)治疗后对单剂抗体或长期治疗后循环HSPC水平的影响。平均而言，在第一次注射Natalizumab后的1天内，循环CD34(+)细胞和集落形成单位培养(CFU-C)的水平平均提高了6倍，而在每月注射Natalizumab的情况下，类似的水平仍然保持不变。接受那他珠单抗治疗的受试者的血液中也含有SCID再生细胞。这些循环中的HSPC的命运以及它们与MS患者的临床相关性仍有待确定。
Blockade of CD49d-mediated lymphocyte trafficking has been used therapeutically for certain autoimmune diseases, such as multiple sclerosis (MS). In addition to negative effects on the trafficking of mature lymphocytes to sites of inflammation, CD49d blockade in mice and monkeys rapidly mobilizes hematopoietic stem/progenitor cells (HSPCs) capable of short and long-term engraftment. Here we aimed to ascertain the effects of treatment with antifunctional anti-CD49d antibody in humans (MS patients receiving infusions of the CD49d-blocking antibody natalizumab) on levels of circulating HSPCs after a single dose of antibody or after long-term treatment. On average, 6-fold elevated levels of circulating CD34(+) cells and colony-forming unit-culture (CFU-C) were achieved within 1 day of the first dose of natalizumab, and similar levels were continuously maintained under monthly natalizumab infusions. The blood of natalizumab-treated subjects also contained SCID-repopulating cells. The fate of these circulating HSPCs and their clinical relevance for MS patients remains to be determined.