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Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Chromosomal radiosensitivity in patients with multiple sclerosis
Maria Milenkova1, Ivan Milanov, Ksenia Kmetska
1III Neurological Clinic, University Hospital Saint Naum, Sofia, Bulgaria.
Abstract:
Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing-remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing-remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing-remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing-remitting multiple sclerosis patients than in healthy controls and relapsing-remitting not treated patients. Intrinsic sensitivity of lymphocytes subpopulations to the apoptotic effect of immunomodulatory treatment could be responsible for this result.
Insights
Multiple sclerosis patients show reduced DNA damage response in lymphocytes compared to healthy individuals. Treated relapsing-remitting multiple sclerosis patients exhibit significantly lower radiation-induced DNA damage, suggesting treatment-induced lymphocyte sensitivity.
Area of Science:
- Immunology
- Genetics
- Neurology
Background:
- Multiple sclerosis (MS) is a complex autoimmune disease causing significant neurological impairment.
- Available disease-modifying therapies for MS have unclear mechanisms of action.
- Understanding lymphocyte radiosensitivity in MS is crucial for treatment evaluation.
Purpose of the Study:
- To investigate radiosensitivity in lymphocytes of patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) compared to healthy controls.
- To assess spontaneous and radiation-induced DNA damage (micronuclei formation) in lymphocytes.
- To explore the impact of immunomodulatory treatments (interferon-β, glatiramer acetate) on lymphocyte radiosensitivity in RRMS patients.
Main Methods:
- Whole blood cultures from MS patients (RRMS, SPMS) and healthy controls were analyzed.
- Micronuclei formation in binucleated lymphocytes was measured to assess spontaneous and gamma-irradiation-induced DNA damage.
- A subgroup of RRMS patients receiving interferon-β or glatiramer acetate was compared with untreated RRMS patients and healthy controls.
Main Results:
- Basal DNA damage levels were comparable across RRMS, SPMS patients, and healthy controls.
- No significant differences in gamma-irradiation-induced micronuclei frequencies were observed between MS patient subtypes and healthy controls.
- A reduction in radiation-induced DNA damage was noted in the overall MS patient group compared to healthy controls.
- Treated RRMS patients showed significantly lower induced micronuclei frequencies than both healthy controls and untreated RRMS patients.
Conclusions:
- Lymphocyte radiosensitivity may be altered in multiple sclerosis patients.
- Immunomodulatory treatments in RRMS appear to enhance lymphocyte sensitivity to radiation-induced DNA damage, possibly via apoptosis.
- These findings suggest a potential mechanism for treatment efficacy and highlight the need for further investigation into lymphocyte subpopulations' responses.
