End stage kidney disease may involve various inflammatory and immune deposition mechanisms. After transplantation, inflammation and antibodies contribute to graft rejection. Important research to understand these mechanisms is supported by a gift from the Dolores Hope Trust.
Central Question in the MNIT's End Stage Kidney Disease Antibody Research
Antibodies deposited in the kidneys can cause tissue damage and kidney failure. One of the central questions in this research is: how do antibodies concentrated in the kidney initiate and cause organ damage.
The MNIT strives to understand how complement enzymes impact renal disease and graft rejection
Antibodies interact with the complement system, triggering a cascade of enzymes that trigger inflammation and attacks cells and tissues. On the other hand, complement plays an important role in solubilizing and removing antibodies and immune complexes from tissues.
As an illustration, not all patients with systemic lupus erythematosus (SLE) develop kidney disease. However, of those who do develop renal involvement, 80% have a deficiency in their complement cascade.
Fc Receptors & Macrophage Ingestion and Destruction of Antibody-Coated Pathogens
Antibodies also interact with macrophages, scavenger cells that roam through normal tissues. They have special receptors on their surface, known as Fc receptors. Fc receptors recognize antibody-coated pathogens and immune complexes.
Genetic deficiencies either in Fc receptors or in the ability of the macrophages to ingest and destroy antibody-coated pathogens leads to failures in clearance of antibodies, immune complexes, and tissues.
The Inflammation Gene Chip
The inflammation resulting from the failure to deal with antibodies and immune complexes is also under genetic control. The MNIT studies a number of candidate genes and is developing an ‘inflammation gene chip’ to gain insight into the damaging inflammation that contributes to kidney failure.