Dr. Athanasios Didangelos is a Rosetrees Trust-funded principal investigator at the University of Leicester, working in the Mayer IgA Nephropathy Laboratory led by Professor Jon Barratt. Their new publication in the Journal of Autoimmunity has identified a new urine marker in IgA Nephropathy (IgAN) known as PEBP4. The protein was found by deep-screening of the urinary proteome by shotgun mass-spectrometry proteomics.
IgAN (a very common kidney disease) can lead to chronic kidney damage and renal failure. A substantial proportion of patients (~20%) end up needing expensive and burdensome dialysis as well as kidney transplants. It is therefore important to identify potential disease markers and/or soluble bioactive factors in IgAN to support early diagnosis and new treatment opportunities. Currently, there are no drugs that can treat IgAN and no biomarkers that can predict disease outcomes.
With the discovery of PEBP4, Dr. Didangelos and his team showed that its concentration is increased in serum and urine of IgAN patients. More importantly, the levels of the soluble protein in urine and serum appeared to positively correlate with the extent of kidney damage in IgAN patients.
The next steps of this research would require further investigation into the role of PEBP4 in kidney pathology. One particular area or interest, is the potential relationship of PEBP4 with B-cells (major disease effectors in IgAN) as well as its likely interplay with a key inflammatory factor named interferon gamma. Importantly, PEBP4 might be involved in inflammatory mechanisms in other diseased organs and tissues.
IgAN is a chronic and progressive disease that affects the kidneys of many thousands of patients in the UK and worldwide. Since there are no treatments for IgAN, these patients have to live for years with a condition that affects a major human organ as well as the devastating uncertainty of whether they will need dialysis or kidney transplantation in the future. I have met multiple IgAN patients and have understood the need to identify new treatment options and clinical prognostic tools for the disease. PEBP4 is a new soluble bioactive candidate that gives us the opportunity to investigate new treatment avenues, specifically targeting important inflammatory cell types (B-cells) and unexplored pathological pathways. Together with Professor Jon Barratt, our work at the Mayer IgA Nephropathy Laboratory, aims to identify new molecules and disease pathways that we can target in much needed future therapies.
Written by: Rebecca Downing and Dr. Athanasios Didangelos