Injury derived autoimmunity: Anti-perlecan/LG3 antibodies in transplantation

Ischemic, immunologic or pharmacological stressors can induce vascular injury and endothelial apoptosis in organ donors, in transplant candidates due to the impact of end stage organ failure on the vasculature, and in association with peri-transplantation events. Vascular injury may shape innate and adaptive immune responses, leading to dysregulation in the balance between tolerance and immunoreactivity to vascular-derived antigens. Mounting evidence shows that the early stages of apoptosis, characterized by the absence of membrane permeabilization, are prone to trigger various modes of intercellular communication allowing neoantigen production, exposure, or both. In this review, we present the evidence for the release of LG3, an immunogenic fragment of perlecan, as a consequence of caspase-3 dependent vascular apoptosis leading to the genesis of anti-LG3 autoantibodies and the consequences of these autoantibodies in native and transplanted kidneys.