A novel immunodeficiency characterized by the exclusive presence of transitional B cells unresponsive to CpG
A novel immunodeficiency characterized by the exclusive presence of transitional B cells unresponsive to CpG
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DOI：
10.1111/j.1365-2567.2006.02556.x
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发表时间：
2007-06-01
期刊：
影响因子：
6.4
通讯作者：
Carsetti, Rita
中科院分区：
文献类型：
--
作者：
Plebani, Alessandro;Lougaris, Vassilios;Carsetti, Rita
本研究的目的是描述一种新的形式的原发免疫疾病，其特征是循环B细胞具有独有的过渡性表型，对CpG刺激不起作用。这名12岁的男性患者从小就患有反复的细菌感染。免疫学研究的基础是广泛的B细胞免疫表型，体内对不同疫苗抗原的体液反应，以及CpG刺激后的体外增殖和免疫球蛋白产生。对IRF8、MyD88、TLR9、T-bet等潜在候选基因进行了序列分析。患者血清免疫球蛋白水平和对破伤风类毒素的特异性抗体反应正常，而对多糖类抗原的反应严重受损。流式细胞仪分析显示，几乎所有患者的外周B细胞都具有过渡性表型(CD24(Bright)、CD38(Bright)、CD27(Neg))。此外，患者的B细胞在体外CpG刺激后不能增殖，也不能分泌免疫球蛋白。TLR9、MyD88、IRF8和T-bet的序列分析未发现突变。据我们所知，这是第一例新的原发免疫缺陷模仿常见变异性免疫缺陷的临床表型，具有特殊的免疫学表型，其特征是免疫球蛋白血清水平正常，具有唯一过渡表型的循环B细胞无法对CpG刺激产生反应。这定义了一种新的形式的原发免疫缺陷，在免疫球蛋白血清水平正常的情况下，模拟常见的可变型免疫缺陷。
The objective of this study was to describe a novel form of primary immune disorder characterized by circulating B cells with the exclusive transitional phenotype which fail to respond to CpG stimulation. The 12-year-old male patient suffered from recurrent bacterial infections since infancy. The immunological studies were based on extensive B cell immunophenotyping, humoral in vivo response to different vaccine antigens, and in vitro proliferation and immunoglobulin production after CpG stimulation. Sequence analysis for potentially candidate genes such as IRF8, MyD88, TLR9, T-bet were performed. The patient's serum immunoglobulin levels and the specific antibody response to tetanus toxoid were normal, whereas that to polysaccharide antigens was severely impaired. Flow cytometric analysis showed that almost all patient's peripheral B cells had the transitional phenotype (CD24(bright) CD38(bright) CD27(neg)). Furthermore, the patient's B cells did not proliferate and failed to secrete immunoglobulins after in vitro CpG stimulation. Sequence analysis for TLR9, MyD88, IRF8 and T-bet showed no mutations. To our knowledge, this is the first case of a novel primary immunodeficiency mimicking the clinical phenotype of common variable immunodeficiency, with a peculiar immunological phenotype characterized by normal immunoglobulin serum levels, circulating B cells with the exclusive transitional phenotype unable to respond to CpG stimulation. This defines a novel form of primary immunodeficiency mimicking common variable immunodeficiency in the presence of normal immunoglobulin serum levels.