Radiosensitivity of Peripheral Blood Lymphocytes in Autoimmune Disease

Abstract

The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. The nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of preirradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studies of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease.

Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors: Literature review and consensus

“…At any rate, the studies that support this statement are retrospective with small numbers of patients and use different scoring scales for complications. As a consequence, these factors may contribute to an overestimation of true radiation-induced morbidity, but the fact that peripheral lymphocytes from patients with lupus erythematosis, RA and systemic sclerosis have significantly greater DNA damage after irradiation than do those from control subjects [40,41]. It is in any case advisable to be prudent in particular when the connective tissue disease is active or associated to an uncontrolled hypertension and type I diabetes [42].…”

Radiation dermatitis: Clinical presentation, pathophysiology, and treatment 2006

“…Peripheral blood lymphocytes from patients with SLE, juvenile RA, and systemic sclerosis have significantly greater DNA damage after irradiation than do those from control subjects. 80,81 Because of this, the presence of connective tissue disease is a relative contraindication to RT.…”

Sensitivity to X-irradiation of Peripheral Blood Lymphocytes from Ageing Donors

“…The effect of exposure to X-ray on the quaternary structure of nuclear DNA of target lymphocytes was assessed as described and discussed previously (Harris et al 1985). Briefly, freshly isolated, unstimulated lymphocytes, non-irradiated or irradiated in air at 0°C with 2 Gy X-rays (1-75 Gy min-) were gently lysed with 'Nonidet' P40 detergent (0-25 per cent) in a solution of 0-25 M sucrose and 3-3 mM CaCl 2 .…”

“…It has been shown previously that peripheral blood lymphocytes from patients with various diseases associated with autoimmunity are hypersensitive to the toxic action of a DNA-methylating agent (N-methyl-N-nitrosourea) (Harris et al 1982) and to X-irradiation (Harris et al 1985). These observations suggest that increased susceptibility to DNA damage associated with its defective repair could play a role in the pathogenesis of autoimmune diseases by increasing the rate of somatic mutations in cells of the immune system.…”

“…The decreased immune responses seen in aged humans and experimental animals include many changes particularly involving thymic dependent functions and increased autoantibody production (Weksler and Siskind 1984). In view of the close association of autoimmune manifestations with ageing, it was considered desirable to investigate the radiosensitivity of peripheral blood lymphocytes in aged individuals in a manner comparable to the study done in younger subjects with autoimmune disease (Harris et al 1985).…”