An international team of researchers from France, Germany, and the U.S. have identified a protein that turns a person’s immune system against itself in the disease membranous nephropathy. The new research was presented at ASN Kidney Week 2014 and published online in the New England Journal of Medicine.
Membranous nephropathy occurs when the small blood vessels in the kidney that filter wastes from the blood are damaged by circulating autoantibodies. As a result, proteins leak from the damaged blood vessels into the urine. For many people, loss of these proteins eventually causes nephrotic syndrome.
Approximately 14% of end-stage renal disease is associated with glomerulonephritis, of which membranous nephropathy is a common form.
This is the second protein associated with membranous nephropathy and the development of an autoimmune response. Through the identification of this second protein, a new blood test can be developed to diagnose and monitor this common form of kidney disease.
In 2009 this international team of scientists reported the discovery of phospholipase A2 receptor 1 (PLA2R1) as the protein targeted by autoantibodies in up to 70% of people suffering from membranous nephropathy. However, the target antigen in the remaining 30% of patients remained unknown.
“This week’s disclosure is related to the discovery of the protein THSD7A and the corresponding anti-THSD7A autoantibodies in a group of about 10% of MN patients who did not have anti-PLA2R1 autoantibodies,” said senior author Gérard Lambeau, PhD, Director of Research at CNRS and team leader at the Institute of Molecular and Cellular Pharmacology (Sophia Antipolis). This finding thus identifies a distinct group of MN patients with anti-THSD7A as a likely biomarker of disease activity.
“The discovery of this second antigen-antibody system in membranous nephropathy will allow clinicians to diagnose this new form of primary (autoimmune) membranous nephropathy and provides a new method to monitor the disease activity in this subgroup of patients,” said co-lead authors Nicola Tomas, MD of University Medical Center Hamburg–Eppendorf and Laurence Beck, MD, PhD, of Boston University School of Medicine.
“Our discovery of PLA2R1 as the target of autoantibodies energized research and accelerated the pace of discovery in this uncommon but serious cause of kidney disease,” said David Salant, MD, chief of nephrology and professor of medicine at Boston University School of Medicine. “Hopefully, our current findings will spur further research to identify the target antigen to benefit the remaining 20% of patients with MN.”
The international research team included collaborators from Nice, France (Nicola M. Tomas, MD, Barbara Seitz-Polski, MD, Guillaume Dolla, MS, Anne-Sophie Dabert-Gay, PhD, Delphine Debayle, PhD, and Gérard Lambeau, PhD, of Centre National de la Recherche Scientifique and Université de Nice Sophia Antipolis, Valbonne); Hamburg, Germany (Catherine Meyer-Schwesinger, MD, Gunther Zahner, PhD, Elion Hoxha, MD, Udo Helmchen, MD, and Rolf A. K. Stahl, MD of University Medical Center Hamburg–Eppendorf); Boston, MA (Laurence H. Beck Jr, MD, PhD, Hong Ma, PhD, David J. Salant, MD, of the Boston University School of Medicine); and Louisville, KY (Jon B. Klein, MD, PhD, and Michael Merchant, PhD of the University of Louisville).
Study: “Identification of Thrombospondin Type 1 Domain Containing 7A as a Novel Antigen in Idiopathic Membranous Nephropathy” (Abstract TH-OR071)