Elevated Level of Oxidative DNA Damage and Impaired DNA Repair Efficiency of PBMCs from Chronic Inflammatory Demyelinating Polyneuropathy
Beata Filipek1, Anna Macieja2, Bhaskar Roy4, Ireneusz Majsterek3, Tomasz Poplawski2
1Department of Pharmaceutical Microbiology and Biochemistry, International Doctoral School Medical University of Lodz, 2Department of Pharmaceutical Microbiology and Biochemistry, 3Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 4Department of Neurology, Yale University
Objective:
Our previous work has suggested impaired DNA repair efficiency in multiple sclerosis (MS), a central demyelinating disease. We examined if a similar pathomechanism is present in CIDP, a demyelinating disease of the peripheral nervous system.
Background:
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease with an orchestrated dysfunction of B and T cells that leads to demyelination of peripheral nerves. Typically, CIDP patients present with symmetric proximal limb weakness and sensory disturbances often accompanied by areflexia.
Design/Methods:
We included five CIDP patients, 30 MS patients and 30 healthy controls. We used an alkaline version of the comet assay (single-cell gel electrophoresis) with modifications to measure sensitivity to DNA-damaging agents and repair efficiency for 60 minutes, measuring the level of DNA damage (Tail DNA %) every 15 minutes after the use of tert-butyl hydroperoxide (TBH).
Results:
We found increased oxidative DNA damage in CIDP and MS patients compared to the controls and observed statistically higher PMBC sensitivity to TBH (MS-25.3%, CIDP-19.57% vs 10.6% in controls, p<0,05). We observed elevated levels of endogenous DNA lesions in CIDP patients that we did not notice in MS patients and controls (CIDP-11.27%, MS- 2.3% vs 2.81% in controls, p<0.05). Examination of the repair kinetics between groups revealed that the DNA lesions induced by TBH were more efficiently repaired in controls than in CIDP and MS patients (p<0.05).
Conclusions:
The preliminary data suggest an elevated level of endogenous oxidative DNA lesions in PBMCs that occurs in CIDP but not in the clinical course of MS. We observed increased susceptibility to oxidative factors and delayed repair efficiency in both of these demyelinating conditions. Further studies are needed to understand the role of DNA damage and repair in peripheral nerve demyelination in CIDP.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.