Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects
Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects
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DOI：
10.1023/a:1025373601374
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发表时间：
2003-09-01
影响因子：
9.1
通讯作者：
Oksenhendler, E
中科院分区：
文献类型：
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作者：
Piqueras, B;Lavenu-Bombled, C;Oksenhendler, E
常见变异型免疫缺陷（CVID）是一种非常异质性的综合征，定义为免疫球蛋白产生受损。基于体外免疫球蛋白产生的CVID患者的功能分类是耗时的，并且从未显示出任何预测价值。我们提出了一个分类的基础上的定量再分配的幼稚/记忆B细胞根据IgD和CD 27的双重表达。将57例患者分为三组：记忆B细胞正常的MB 2组（11例患者，19%）;转换记忆（IgD（-）CD 27（+））缺陷但非转换记忆B细胞正常（IgD（+）CD 27（-））的MB 1组（19例患者，33%）;几乎无记忆B细胞的MB 0组（27例患者，47%）。此外，B细胞上活化标志物（CD 25、CD 21、CD 80、CD 86）的表达降低是MB 1组患者的特征，并且与T细胞上活化标志物（HLA-DR、CD 95、CD 57）的表达升高相关。该分类与一些临床方面相关，显示MB 0组中脾肿大（16/27，59%）、淋巴样增生（13/27，48%）和肉芽肿性疾病（12/27，44%）的患病率较高。脾肿大在MB 1组也很常见（8/19，42%）。相反，在所有三组中观察到的自身免疫的患病率相似。此外，通过分析B细胞表型，免疫球蛋白转录表达，和体细胞突变，我们提出了不同的推定机制负责受损的B细胞活化和记忆分化，在这种综合征。
Common variable immunodeficiency (CVID) is a very heterogeneous syndrome defined by impaired immunoglobulin production. The functional classification of CVID patients on the basis of in vitro immunoglobulin production is time consuming and has never shown any predictive value. We propose a classification based on the quantitative repartition of naive/memory B cells according to the dual expression of IgD and CD27. Fifty-seven patients were categorized into three groups: Group MB2 (11 patients, 19%) with normal memory B cells; Group MB1 (19 patients, 33%) with defective switched memory (IgD(-)CD27(+)) but normal nonswitched memory B cells (IgD(+)CD27(-)); Group MB0 (27 patients, 47%) with almost no memory B cells. In addition, a downexpression of activation markers (CD25, CD21, CD80, CD86) on B cells characterized the group MB1 patients and was associated with an upexpression of activation markers (HLA-DR, CD95, CD57) on T cells. This classification correlates with some clinical aspects showing a higher prevalence of splenomegaly (16/27, 59%), lymphoid proliferation (13/27, 48%) and granulomatous disease (12/27, 44%) in group MB0. Splenomegaly was also frequent in group MB1 (8/19, 42%). In contrast, autoimmunity was observed with similar prevalence in all three groups. Moreover, by analyzing B cell phenotype, immunoglobulin transcript expression, and somatic mutations, we propose different putative mechanisms responsible for impaired B cell activation and memory differentiation in this syndrome.