Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56∓dim chronic natural killer cell large granular lymphocytosis
Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56∓dim chronic natural killer cell large granular lymphocytosis
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DOI：
10.1016/s0002-9440(10)63373-1
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发表时间：
2004-10-01
影响因子：
6
通讯作者：
Orfao, A
中科院分区：
文献类型：
--
作者：
Lima, M;Almeida, J;Orfao, A
惰性自然杀伤（NK）细胞淋巴增殖性疾病包括一组异质性的患者，在没有任何克隆标记的情况下，外周血中存在成熟的、典型的CD56(+) NK细胞的持续扩增。在本研究中，我们报告了一系列26例慢性大颗粒NK细胞淋巴细胞增多症患者的临床、血液学、免疫表型、血清学和分子特征，这些患者的NK细胞要么是CD56(-)，要么表达非常低水平的CD56（CD56(-/+dim) NK细胞），在异常激活相关的成熟表型的背景下，使用基于人雄性激素受体基因聚合酶链反应的方法证明是单克隆的。与正常的CD56+ NK细胞一样，CD56(-/+dim) NK细胞是颗粒酶B+、CD3（-）、tcrα β / γ(-)、CD5（-）、CD28（-）、CD11a（+bright）、CD45RA（+bright）、CD122（+）和CD25(-)，它们表达CD8和CD57的表达是可变的和异质的。然而，他们表现出一些不寻常的免疫表型特征。因此，除了CD56外，它们还是CD11b（-/+暗）（异质）、CD7（-/+暗）（异质）、CD2(+)（均质）、CD11c（+亮）（均质）和CD38（-/+暗）（均质）。此外，CD56(-/+dim) NK细胞异质表达HLA-DR。在杀伤受体的表达方面，CD56(-/+dim) NK细胞对CD94的表达为亮质且均匀，对CD161的表达为暗质且不均匀，而CD158a和NKB1的表达则是可变的。从功能角度来看，CD56（-/+dim）表现出典型的Th1模式的细胞因子产生(干扰素- γ（+)，肿瘤坏死因子- α(+)）。从临床角度来看，这些患者通常有一个缓慢的临床过程，只有一例进展为大量淋巴细胞增生并肺浸润导致死亡。尽管如此，他们经常有相关的细胞减少症以及肿瘤疾病和/或病毒感染。总之，我们描述了一组独特而均匀的单克隆慢性大颗粒NK细胞淋巴细胞病，具有异常活化相关的CD56(-/+dim)/CD11b（-/+dim）表型和惰性临床病程，其主要临床特征与伴随疾病有关。
Indolent natural killer (NK) cell lymphoproliferative disorders include a heterogeneous group of patients in whom persistent expansions of mature, typically CD56(+), NK cells in the absence of any clonal marker are present in the peripheral blood. in the present study we report on the clinical, hematological, immunophenotypic, serological, and molecular features of a series of 26 patients with chronic large granular NK cell lymphocytosis, whose NK cells were either CD56(-) or expressed very low levels of CD56 (CD56(-/+dim) NK cells), in the context of an aberrant activation-related mature phenotype and proved to be monoclonal using the human androgen receptor gene polymerase chain reaction-based assay. As normal CD56+ NK cells, CD56(-/+dim) NK cells were granzyme B+, CD3(-), TCRalphabeta/gammadelta(-), CD5(-), CD28(-), CD11a(+bright), CD45RA(+bright), CD122(+), and CD25(-) and they showed variable and heterogeneous expression of both CD8 and CD57. Nevertheless, they displayed several unusual immunophenotypic features. Accordingly, besides being CD56 they were CD11b(-/+dim) (heterogeneous), CD7(-/+dim) (heterogeneous), CD2(+) (homogeneous), CD11c(+bright) (homogeneous), and CD38(-/+dim) (heterogeneous). Moreover, CD56(-/+dim) NK cells heterogeneously expressed HLA-DR. In that concerning the expression of killer receptors, CD56(-/+dim) NK cells showed bright and homogeneous CD94 expression, and dim and heterogeneous reactivity for CD161, whereas CD158a and NKB1 expression was variable. From the functional point of view, CD56(-/+dim) showed a typical Th1 pattern of cytokine production (interferon-gamma(+), tumor necrosis factor-alpha(+)). From the clinical point of view, these patients usually had an indolent clinical course, progression into a massive lymphocytosis with lung infiltration leading to death being observed in only one case. Despite this, they frequently had associated cytopenias as well as neoplastic diseases and/or viral infections. in summary, we describe a unique and homogeneous group of monoclonal chronic large granular NK cell lymphocytosis with an aberrant activation-related CD56(-/+dim)/CD11b(-/+dim) phenotype and an indolent clinical course, whose main clinical features are related to concomitant diseases.