Impact of ApoExo vesicules and Anti-LG3 autoantibodies derived from vascular damage on microvascular depletion, fibrosis and renal dysfunction in the context of lupus nephretis

Systemic lupus erythematosus (SLE) is an autoimmune disease, in which the body’s immune system attacks its own cells and organs. One of the attacked organs is the kidney, leading to a disease called lupus nephritis (LN). LN is a serious manifestation, affecting 60% of adults with SLE. The attacked kidneys are then unable to filter waste products from the blood properly. About 30% of patients progress to end-stage renal disease where the kidneys no longer work. Patients then must go on dialysis or have a transplant to survive. During LN, the immune system attacks the blood vessels that deliver oxygen and nutrients to the kidneys. Our group has shown that attacked blood vessels, when they die, release messengers that can alert the immune system and induce the production of autoantibodies, antibodies directed against molecules of the individual himself. One of these molecules, “LG3”, is found on micro-vessels. Our group has also demonstrated that the autoantibodies directed against LG3, the anti-LG3, were important actors in the loss of micro-vessels in several kidney diseases and in the rejection of transplants. We have also demonstrated that anti-LG3 autoantibodies measured after kidney transplantation are associated with severe vascular rejection and that pre-transplant anti-LG3 levels are also associated with acute vascular rejection of renal allografts. We have found that these anti-LG3s were present in greater amounts in the blood of patients with LN as well as in mice with lupus. The objective of my project is to characterize the impact of anti-LG3 attack on kidney micro-vessels to identify new mechanisms and predictors of renal dysfunction. My project provides a unique opportunity to identify new intervention targets to develop tests and therapies that will help monitor
and treat patients with LN to prevent the devastating effects of this disease and the need for transplantation.