Background: Lipid peroxidative-mediated reactions have been implicated in alopecia areata (AA). However, the potential for lipid peroxidation to elicit an autoimmune response or to contribute in disease pathogenesis remain unexplored. This study was undertaken to investigate the status/contribution of lipid oxidative-by-product malondialdehyde modified DNA (MDA-DNA) in AA.
Methods: DNA was modified by MDA. Binding characteristics of AA circulating immunoglobulin G (AA-IgG) MDA-modified DNA were screened. Immunogenicity of MDA-DNA was probed by inducing antibodies in rabbits. DNA samples from AA patients were isolated (DNA-AA) and their immune reactions with rabbit anti-MDA-DNA-IgGs were evaluated.
Results: Our data show that MDA caused extensive DNA damage. Protein-A purified IgG from 45% of AA patients showed strong binding to MDA-DNA in comparison with native DNA (p < 0.05). MDA-DNA was found to be highly immunogenic in rabbits. Rabbit anti-MDA-DNA-IgG showed binding with isolated DNA from AA patients.
Conclusions: This is the first study to demonstrate the role of MDA-modified DNA in AA patients. Our novel results conclude that perturbations in DNA by MDA present unique neo-epitopes that might be one of the factors for the antigen driven antibodies induction in AA. These results provide an important insight into the immunological mechanisms occurring in AA.
Keywords: Alopecia areata; DNA; anti-MDA-DNA antibodies; autoimmunity; lipid peroxidation.