Farrar J E, Rohrer J, Conley M E
Department of Pediatrics, University of Tennessee College of Medicine, Memphis 38103, USA.
Clin Immunol Immunopathol. 1996 Dec;81(3):271-6. doi: 10.1006/clin.1996.0188.
X-linked agammaglobulinemia (XLA) is usually considered a disorder of B cell development; however, the gene that is defective in XLA encodes a cytoplasmic tyrosine kinase called Btk, that is expressed throughout myeloid as well as B cell differentiation. A review of medical records of patients in whom mutations in Btk had been identified indicated that 13 of 50 patients (26%) had experienced episodes of profound neutropenia. In 12 of the 13 patients, neutropenia was part of the acute illness that precipitated an evaluation for immunodeficiency. These boys were more likely to be less than a year of age at the time of diagnosis and they were less likely to have a family history of immunodeficiency. Neutropenia was associated with staphylococcal or pseudomonas sepsis in 6 of the patients. The duration of neutropenia was variable but was often more than 1 week. Neutropenia was not seen in any patient with XLA receiving intravenous gammaglobulin. Although neutropenia was not associated with any specific mutation in Btk, most of the alterations in this gene in the patients with XLA and neutropenia resulted in the absence of Btk protein or in amino acid substitutions in sites thought to be critical to Btk function. Btk may not be required for neutrophil production under normal circumstances; however, it may play a role in the response to stress.
X连锁无丙种球蛋白血症（XLA）通常被认为是一种B细胞发育障碍；然而，XLA中存在缺陷的基因编码一种名为Btk的细胞质酪氨酸激酶，该激酶在髓系以及B细胞分化过程中均有表达。对已确定存在Btk突变的患者病历进行回顾发现，50名患者中有13名（26%）曾经历过严重中性粒细胞减少发作。在这13名患者中的12名中，中性粒细胞减少是促使对免疫缺陷进行评估的急性疾病的一部分。这些男孩在诊断时年龄更可能小于1岁，且他们有免疫缺陷家族史的可能性较小。6名患者的中性粒细胞减少与葡萄球菌或假单胞菌败血症有关。中性粒细胞减少的持续时间各不相同，但通常超过1周。接受静脉注射丙种球蛋白的任何XLA患者均未出现中性粒细胞减少。虽然中性粒细胞减少与Btk中的任何特定突变均无关联，但XLA合并中性粒细胞减少患者中该基因的大多数改变导致Btk蛋白缺失或在被认为对Btk功能至关重要的位点出现氨基酸替代。在正常情况下，中性粒细胞生成可能不需要Btk；然而，它可能在应激反应中发挥作用。
