IDENTIFICATION of a protein, thrombospondin type-1 domain-containing protein 7A (THSD7A), that turns a person’s immune system against itself in sufferers of membranous nephropathy (MN) could give patients a fighting chance now that a blood test can be developed to diagnose and monitor this prevalent type of kidney disease.
MN is caused by the gradual build-up of circulating autoantibodies which damage the small blood vessels in the kidney, hindering waste filtration from the blood. This results in protein leakage from damaged blood vessels into urine, which can lead to development of nephrotic syndrome in many cases.
Kidney failure or end-stage renal disease (ESRD) can be the detrimental result of unchecked MN. It is estimated that 14% of ESRD is associated with glomerulonephritis, of which MN is a common form.
An international team of scientists were responsible for the discovery of the first protein, phospholipase A2 receptor 1 (PLA2R1) in 2009, which is targeted by autoantibodies in up to a staggering 70% of MN sufferers; yet, for the remaining 30% of patients, a target antigen remains unknown.
According to Dr Gérard Lambeau, Director of Research, The National Centre for Scientific Research, and team leader, Institute of Molecular and Cellular Pharmacology, Nice, France, the discovery of THSD7A, and its corresponding anti-THSD7A autoantibodies, can account for approximately 10% of those MN patients who did not have anti-PLA2R1 autoantibodies; additionally, anti-THSD7A can potentially be used as a biomarker in assessing disease activity.
“Our discovery of PLA2R1 as the target of autoantibodies energised research and accelerated the pace of discovery in this uncommon but serious cause of kidney disease,” said Dr David Salant, Chief of Nephrology and Professor of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
“Hopefully, our current findings will spur further research to identify the target antigen to benefit the remaining 20% of patients with MN .”