Preferential recognition of hydroxyl radical-modified superoxide dismutase by circulating autoantibodies in patients with alopecia areata

Abstract

Background: Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The cause of AA is unknown but reports suggest an autoimmune etiology, where oxygen free radicals play an important role. Objective: The aim of this study was to investigate the role of a hydroxyl radicals (•OH)-modified antioxidant enzyme, superoxide dismutase (SOD), in AA autoimmunity. Methods: SOD was modified by •OH radicals. Binding characteristics of autoantibodies in AA patients (n=26) against •OH-modified SOD (•OH-SOD) were evaluated by immunoassays and the results were compared with those of healthy, age-matched controls (n=30). The effects of •OH radicals on immunoglobulin G (IgG) isolated from AA patients were studied. Results: Highly specific binding to •OH-SOD was observed in 32% of the samples of patient sera, whereas normal human sera showed negligible binding with either antigen. Competitive inhibition immunoassays reiterated the results from direct binding. Protein-A-purified IgG from AA patients (AA-IgG) also showed strong binding to •OH-SOD as compared to IgG from normal human controls (<0.001). In addition, AA-IgG from patients with alopecia universalis recognized •OH-SOD to a greater extent than did AA-IgG from patients with the patchy, persistent type of alopecia. Furthermore, sera from AA patients had lower levels of SOD activity as compared to control sera. Conclusion: This is the first report showing an association between •OH-modified SOD and AA. These novel results demonstrate that •OH radical-mediated changes in SOD present unique neo-epitopes that might contribute to antigen-driven antibody induction in AA.