Antibodies to the phospholipase A2 receptor (PLA2R) occur in 70% to 80% of patients with primary membranous nephropathy, an autoimmune disease characterized by accumulating immune complexes in the renal glomeruli. It is the most common cause of nephrotic syndrome in adults.
Detecting antibodies in serum is crucial for diagnosing primary membranous nephropathy and may make a kidney biopsy unnecessary. In addition, measuring the autoantibodies can monitor disease activity and therapy response.
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Anti-phospholipase A2 Receptor (anti-PLA2R) autoantibodies target the phospholipase A2 receptor, a protein found on the surface of podocytes, cells in the kidneys. These autoantibodies are associated with a kidney disease known as idiopathic membranous nephropathy (IMN). IMN is a primary glomerular disease characterized by the thickening of the glomerular basement membrane, leading to proteinuria (the presence of excess proteins in the urine) and impaired kidney function. Membranous nephropathy (MN) is a rare disease in which immune complexes deposit at the glomerular basement membrane, causing damage to the filtration barrier and resulting in proteinuria. Recent studies have shown that in approximately 50% to 80% of adult patients with primary MN and a lesser proportion of affected children, the immune complexes consist of autoantibodies against the podocyte protein M-type phospholipase A2 receptor (PLA2R). These antibodies are not present in the serum of healthy controls or patients with other kidney or systemic diseases, yielding a 100% specificity for the lesion of MN. Less frequently (in up to 10%), antibodies against thrombospondin type-1 domain-containing 7A (THSD7A) are determined.
The phospholipase A2 receptor regulates immune responses, and its dysfunction or the presence of autoantibodies against it can contribute to the development of autoimmune diseases such as IMN. The exact mechanisms by which anti-PLA2R autoantibodies contribute to kidney damage are not fully understood, but it is believed that the binding of these antibodies to the receptor triggers an immune response that leads to inflammation and damage to the kidney glomeruli.
The detection of anti-PLA2R antibodies in the blood can be used as a diagnostic marker for IMN. It is also helpful in monitoring disease activity and assessing the response to treatment. Treatment for IMN may include immunosuppressive medications to reduce the autoimmune response and manage symptoms.
It's important to note that while anti-PLA2R antibodies are a standard marker for IMN, not all IMN cases are associated with these antibodies' presence. Some individuals with IMN may have other types of antibodies, and the understanding of the disease is evolving as research continues.
More Information on Phospholipase A2 receptor
PLA2R is a type I transmembrane receptor and is one of four mammalian mannose receptor family members. It is an 185-kDa protein that is expressed on and confined to the surface of human podocytes. Circulating PLA2R has not been identified. PLA2R has a conserved domain structure with most receptors located extracellularly and short membrane-spanning. The receptor is constantly recycled through endocytosis, possibly providing an ongoing source of accessible PLA2R to serve as a target for immune complex formation. The nephritogenic epitope of PLA2R depends on intramolecular disulfide bonds in the methionine-rich extracellular domain; autoantibody formation depends on this particular conformation. The physiologic function of human PLA2R remains unclear.
