Antibodies Against Anti-Oxidant Enzymes in Autoimmune Glomerulonephritis and in Antibody-Mediated Graft Rejection

Résumé fourni par la source

Historically, oxidants have been considered mechanisms of glomerulonephritis, but a direct cause-effect correlation has never been demonstrated. Several findings in the experimental model of autoimmune conditions with renal manifestations point to the up-regulation of an oxidant/anti-oxidant system after the initial deposition of autoantibodies in glomeruli. Traces of oxidants in glomeruli cannot be directly measured for their rapid metabolism, while indirect proof of their implications is derived from the observation that Superoxide Oxidase 2 (SOD2) is generated by podocytes after autoimmune stress. The up-regulation of other anti-oxidant systems takes place as well. Here, we discuss the concept that a second wave of antibodies targeting SOD2 is generated in autoimmune glomerulonephritis and may negatively influence the clinical outcome. Circulating and renal deposits of anti-SOD2 antibodies have been detected in patients with membranous nephropathy and lupus nephritis, two main examples of autoimmune disease of the kidney, which correlate with the clinical outcome. The presence of anti-SOD2 antibodies in circulation and in the kidney has been interpreted as a mechanism which modifies the normal tissue response to oxidative stress. Overall, these findings repropose the role of the oxidant/anti-oxidant balance in autoimmune glomerulonephritis. The same conclusion on the oxidant/anti-oxidant balance may be proposed in renal transplant. Patients receiving a renal graft may develop antibodies specific for Glutathione Synthetase (GST), which modulates the amount of GST disposable for rapid scavenging of reactive oxygen species (ROS). The presence of anti-GST antibodies in serum is a major cause of rejection. The perspective is to utilize molecules with known anti-oxidant effects to modulate the anti-oxidative response in autoimmune pathology of the kidney. A lot of molecules with known anti-oxidant effects can be utilized, many of which have already been proven effective in animal models of autoimmune glomerulonephritis. Many molecules with anti-oxidant activity are natural products; in some cases, they are constituents of diets. Owing to the simplicity of these drugs and the absence of important adverse effects, many anti-oxidants could be directly utilized in human beings.

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