Function and X Chromosome Inactivation Analysis of B Lymphocytes in Myelodysplastic Syndromes with Immunological Abnormalities
Function and X Chromosome Inactivation Analysis of B Lymphocytes in Myelodysplastic Syndromes with Immunological Abnormalities
复制标题
免疫异常骨髓增生异常综合征B淋巴细胞的功能及X染色体失活分析
作者：
M. Okada;T. Okamoto;Y. Takemoto;A. Kanamaru;E. Kakishita
为探讨骨髓增生异常综合征（MDS）免疫异常（IA）的发病机制，我们检测了B细胞产生细胞因子的能力及其X染色体失活模式（XCIP）。IA定义为至少一项自身免疫实验室检查（如抗核抗体、类风湿因子）呈阳性。73例MDS患者[65例难治性贫血（RA），3例RA伴原始细胞过多（RAEB），5例RAEB转化]进行了检查; 47例IA，26例无IA。为了检测B细胞在MDS中的功能，在有或没有刺激物的纯化B细胞培养物中测量白细胞介素（IL）-6和IL-10的产生。IA患者IL-6和IL-10的产生率均显著高于非IA患者和正常对照组。用聚合酶链反应分析B细胞XCIP的偏斜情况，并以对照T淋巴细胞为对照，定量测定B细胞XCIP的偏斜率。IA组B细胞的偏位率高于非IA组和正常对照组。因此，IA患者中的一小部分B细胞可能来源于MDS克隆，并与IA的诱导有关。
To investigate the pathogenesis of immunological abnormalities (IA) in myelodysplastic syndrome (MDS), we examined B cells for their ability to produce cytokine and their X chromosome inactivation pattern (XCIP). An IA was defined as being positive for at least one autoimmune laboratory test (e.g. antinuclear antibody, rheumatoid factor). Seventy-three MDS patients [65 with refractory anemia (RA), 3 with RA with excess blasts (RAEB), and 5 with RAEB in transformation] were examined; 47 had IA and 26 had no IA. To examine the function of B cells in MDS, the production of interleukin (IL)-6 and IL-10 was measured in cultures of purified B cells with or without stimulators. Both IL-6 and IL-10 production rates in patients with IA were significantly higher than in patients without IA and normal controls. The skewing of XCIP of B cells was analyzed by using the polymerase chain reaction, and the skewing rate of B cell XCIP was quantitatively assayed by compared to control T lymphocytes. The skewing rate of B cells was higher in patients with IA than in those without IA and normal controls. Therefore, a small population of B cells in patients with IA might be derived from MDS clones, and be associated with the induction of IA.