Mosaicism of NK cells in a patient with Wiskott-Aldrich syndrome
Mosaicism of NK cells in a patient with Wiskott-Aldrich syndrome
复制标题
DOI：
10.1182/blood-2004-12-4724
复制
发表时间：
2005-10-15
期刊：
影响因子：
20.3
通讯作者：
Remold-O'Donnell, E
中科院分区：
文献类型：
--
作者：
Lutskiy, MI;Beardsley, DS;Remold-O'Donnell, E
罕见的由遗传突变逆转引起的体细胞嵌合体病例可导致血细胞疾病的减弱，包括Wiskott-Aldrich综合征（WAS）。回复突变造血干细胞或祖细胞的影响，特别是它们在血细胞群体中的代表性，是令人感兴趣的，因为它预测了基因治疗的结果。在这里，我们报告了一个8岁的病人与WASP基因，废除蛋白质表达的单核苷酸插入引起的WAS。尽管如此，患者病情轻微。我们在一部分患者淋巴细胞中发现了突变的逆转。40%的自然杀伤（NK）细胞表达Wiskott-Aldrich综合征蛋白（WASP），NK细胞含有突变和回复突变（正常）序列。WASP在患者T或B细胞中不表达; T细胞仅含有突变序列。WASP（+）NK细胞的选择性优势也被证明为携带者女性。WASP（+）-回复突变NK细胞的富集表明，WASP在该谱系中提供了选择性优势，并预测了重建NK细胞区室的基因治疗的成功。重建的NK细胞谱系的重要性进行了讨论。
Rare cases of somatic mosaicism resulting from reversion of inherited mutations can lead to the attenuation of blood-cell disorders, including Wiskott-Aldrich syndrome (WAS). The impact of the revertant hematopoietic stem or progenitor cells, particularly their representation in blood-cell populations, is of interest because it predicts the outcome of gene therapy. Here we report an 8-year-old patient with WAS caused by a single nucleotide insertion in the WASP gene that abrogates protein expression. The patient nonetheless had mild disease. We found reversion of the mutation in a fraction of patient lymphocytes. Forty percent of natural killer (NK) cells expressed Wiskott-Aldrich syndrome protein (WASP), and NK cells contained both mutated and revertant (normal) sequences. WASP was not expressed in patient T or B cells; T cells contained only the mutated sequence. The selective advantage of WASP(+) NK cells was also demonstrated for carrier females. The enrichment of WASP(+)-revertant NK cells indicates that WASP provides a selective advantage in this lineage and predicts the success of gene therapy for reconstituting the NK-cell compartment. The importance of reconstituting the NK-cell lineage is discussed.