Redox-Reactive Autoantibodies: Biochemistry, Characterization, and Specificities

Oxidation–reduction (redox) reactions can “unmask” autoantibody activity in blood and other body fluids from normal, healthy individuals. These “unmasked” autoantibodies are similar if not identical to autoantibodies associated with autoimmune diseases. The agents responsible for this unmasking are physiological oxidants such as hemin and likely other naturally occurring molecules in the body that contain transitional metals available for participation in redox reactions. Laboratory comparisons between oxidized and non oxidized IgG fail to show differences to account for the oxidation-induced alteration of antibody specifics. The autoantibodies unmasked by redox reactivities represent a growing list of specificities, many that are responsible for modulating and/or regulating intracellular functions. In contrast, alloantibodies, such as anti-HLA antibodies, do not exhibit susceptibility to oxidation-induced autoantibody alterations, suggesting differences in the amino acids responsible for forming the complementarity determining regions of these respective antibody molecules. We have proposed that such reversible oxidative conversions of antibody reactivities represent a heretofore undiscovered, but an evolutionary-conserved, resource of innate humoral immunity destined to maintain an immunological homeostasis.