Department of Hematology, Spedali Civili, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
J Transl Med. 2010 Nov 5;8:111. doi: 10.1186/1479-5876-8-111.
The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes.
The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs) and T-cell receptor excision circles (TRECs) by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test.
KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype.
The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.
慢性淋巴细胞白血病中出现的免疫缺陷导致频繁发生感染和自身免疫现象，并且可能参与恶性克隆的启动和维持。在这里，我们通过实时 PCR 分析定量评估了慢性淋巴细胞白血病患者和健康对照中新产生的 B 和 T 淋巴细胞的缺陷。
通过实时 PCR 分析同时检测两个靶点的方法，定量检测 κ 缺失重组切除环 (KRECs) 和 T 细胞受体切除环 (TRECs)，分析慢性淋巴细胞白血病患者和健康对照中新产生的 B 和 T 淋巴细胞在产生和成熟部位的输出。通过六色流式细胞术分析 T 淋巴细胞亚群。采用双侧曼-惠特尼检验进行数据比较。
在疾病的早期，未经治疗的慢性淋巴细胞白血病患者的 KRECs 水平降低，而 TRECs+细胞的释放得到保留。此外，观察到的 CD4+淋巴细胞增加可归因于效应记忆表型 CD4+细胞的积累。
这些患者新产生的 B 淋巴细胞数量减少可能与免疫系统平衡异常 B 细胞扩增的一种稳态机制有关。这一特征可能先于疾病后期特征性的体液免疫严重缺陷。
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