Vorechovský I, Scott D, Haeney M R, Webster D A
Karolinska Institute, Center for BioTechnology, Huddinge, Sweden.
Mutat Res. 1993 Dec;290(2):255-64. doi: 10.1016/0027-5107(93)90166-d.
From more than 500 tumours reported in human primary immune deficiencies a majority has been observed in two disorders: ataxia telangiectasia (A-T) and common variable immune deficiency (CVID). Since both diseases have an increased risk of lymphomas/leukaemias and gastrointestinal tumours, suggesting a common risk factor, and the cells derived from A-T patients exhibit an increased chromosomal radiosensitivity we analysed chromosome damage in the G2 lymphocytes of 24 CVID patients and 21 controls after X-irradiation in vitro. There was a significant difference in mean aberration yields between patients and controls. Three CVID patients had yields higher than the mean + 3SD of the controls. Six patients but only one control had yields higher than the mean + 2SD of controls. The patient with the highest chromosomal radiosensitivity subsequently developed a lymphoma. Repeat assays on the same blood sample, with a 24-h delay in setting up the second culture, showed as much variability for control donors as the variation between control donors although for CVID patients inter-individual variation was greater than the difference between results of repeat samples. There was a weak positive correlation between radiosensitivity and age of donor. Chromosomal radiosensitivity of five patients with X-linked hypogammaglobulinaemia was not different from healthy donors. The mean mitotic index (MI) for unirradiated samples from CVID patients was significantly lower than for controls and there was an inverse relationship between MI and aberration yields in the patients, but not in controls. We suggest that the defect in CVID patients that reduces response to mitogenic stimuli may have mechanism(s) in common with those involved in cellular repair processes.
在人类原发性免疫缺陷中报告的500多种肿瘤中，大多数出现在两种疾病中：共济失调毛细血管扩张症（A-T）和常见变异型免疫缺陷（CVID）。由于这两种疾病患淋巴瘤/白血病和胃肠道肿瘤的风险增加，提示存在共同的风险因素，并且来自A-T患者的细胞表现出更高的染色体放射敏感性，因此我们分析了24例CVID患者和21例对照的G2淋巴细胞在体外X射线照射后的染色体损伤。患者和对照之间的平均畸变率存在显著差异。3例CVID患者的畸变率高于对照的平均值+3个标准差。6例患者但只有1例对照的畸变率高于对照平均值+2个标准差。染色体放射敏感性最高的患者随后发生了淋巴瘤。对同一血样进行重复检测，在建立第二次培养时延迟24小时，结果显示对照供体的变异性与对照供体之间的变异性一样大，尽管CVID患者的个体间变异性大于重复样本结果之间的差异。放射敏感性与供体年龄之间存在弱正相关。5例X连锁低丙种球蛋白血症患者的染色体放射敏感性与健康供体无差异。CVID患者未照射样本的平均有丝分裂指数（MI）显著低于对照，并且患者中MI与畸变率之间存在负相关，但对照中不存在。我们认为，CVID患者中降低对有丝分裂刺激反应的缺陷可能与细胞修复过程中涉及的机制有共同之处。
