The candidate for this Clinical Scientist Development Award is a pediatric nephrologist who will use this work towards establishing an independent research program. The work will be conducted in the Institute of Molecular Medicine and in the Department of Pediatrics at The University of Texas Health Science Center at Houston. The goal of the proposed research is to define and study the role of a novel receptor for immune complexes on resident cells lining blood vessels within the mouse kidney. Immune complexes in the blood preferentially accumulate in the kidney in many inflammatory diseases, including systemic lupus erythematosus, IgA nephropathy, cryoglobulinemia, serum sickness and sepsis. Elucidating the mechanisms of accumulation and clearance is essential for accurately diagnosing and treating these forms of glomerulonephritis. CD300g is a novel immune complex receptor expressed on endothelial cells. The expression and function of CD300g will be studied in vitro and in vivo. Primary renal endothelial cell have been isolated and cultured, which serve as a unique resource. Specificity will be addressed using the available CD300g knock out mouse.
The aims of the research plan are to 1) study the role of CD300g in immune complex binding by renal endothelial cells, 2) study the endothelial cell responses to immune complex binding in vitro, and 3) validate markers of CD300g activation by immune complexes in a mouse model of acute renal immune complex accumulation. Results will provide the foundation for future investigation on mechanisms of immune complex diseases of the kidney.
Immune complexes accumulate in the kidneys in 45-65% of patients with glomerulonephritis. Glomerulonephritis is an important cause of renal failure. This work will provide new avenues for approaching the diagnosis and management of these diseases, with potential to help preserve kidney function. This could reduce the burden of end stage renal disease and avoid the need for dialysis in a significant set of patients.
