In vitro chromosomal radiosensitivity in patients with common variable immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is one of the predominant antibody deficiency disorders, some evidence of which indicates that chromosome instability is present in these patients. An increased risk of cancer in patients with CVID has been documented. This study was undertaken to highlight radiation sensitivity in CVID patients and to clarify the genetic basis of this defect in these cases. Stimulated lymphocytes of the studied subjects were exposed to low-dose gamma-rays in the G2 phase or the G0 phase of the cell cycle and chromosomal aberrations were scored. Lymphocytes of healthy individuals, ataxia telangiectasia (AT) cases and a group of acute lymphoblastic leukemia (ALL) patients were investigated in the same way as controls. By two methods of analysis (one-way ANOVA and unpaired t-test), the CVID cases were significantly more radiosensitive than healthy controls based on the results of the G2 and the G0 assays. First-degree relatives of CVID patients were radiosensitive by the micronucleus assay which showed a significant difference as compared with normal controls (p = 0.001). In conclusion, this study may support that chromosomal radiosensitivity in CVID patients is a marker of genetic predisposition to the disease. The results might be a clue to describe the increased risk of cancer in CVID patients.

Keywords: acute lymphoblastic leukemia; ataxia telangiectasia; chromosome radiosensitivity; common variable immunodeficiency; primary immunodeficiency.

Fig. 1

Metaphase spread in peripheral blood lymphocytes after low dose rate γ-radiation exposure from a common variable immunodeficiency patient with a significant number of chromatid breaks, chromosome breaks and chromosome exchange noted. CT.b – chromatid break; Cb – chromosome break; Cg – chromosome gap; C.exch – chromosome exchange

Fig. 2

Correlation between G2 score (chromatid breaks + chromatid gaps) and micronucleus yield in peripheral blood lymphocytes of common variable immunodeficiency (CVID) patients or of a healthy control group after low dose rate exposure of γ-irradiation. A poor correlation was found between the G2 and the G0 assays in both CVID patients and healthy control groups (r = 0.28, p = 0.12 and r = 0.27, p = 0.14, respectively)