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Phospholipase Receptor A2 Antibody

Membranous nephropathy causes 15 to 30% of the cases of nephrotic syndrome in nondiabetic adults. The idiopathic form of the disease is characterized by diffuse thickening of the glomerular basement membrane due to binding of IgG and C3. Approximately 70% of cases are associated with autoantibodies binding to the phospholipase A2 receptor on glomerular podocytes. Autoantibodies are predominantly of the IgG4 subclass. Because these autoantibodies are not detected in secondary causes of membranous nephropathy due to systemic lupus erythematosis, hepatitis B, malignancy or some drugs this test can be used to differentiate primary membranous nephropathy from other causes.

In patients with clinical features of membranous nephropathy, definitive diagnosis is made by examining a kidney biopsy and staining for the anti-phospholipase A2 receptor (PLA2R) antibody, C1q, and IgG subclasses. Increased staining for anti-PLA2R and IgG4 predominance are consistent with primary membranous nephropathy. The sensitivity and specificity of PLA2R staining on kidney biopsies for adult primary membranous nephropathy are 70% and 83%, respectively. PLA2R staining has much lower sensitivity (45%) in cases of childhood primary membranous nephropathy.

PLA2R staining is negative in almost all cases of membranous nephropathy due to lupus but positive in approximately 25% of cases of membranous nephropathy associated with malignancy, 75% of cases associated with sarcoidosis, and 64% of cases associated with hepatitis C virus infection. In patients who have received a kidney transplant, PLA2R staining is positive in 83% of cases of recurrent membranous nephropathy.

Ten percent of patients with PLA2R-negative primary membranous nephropathy have antibodies directed against another podocytes antigen, thrombospondin type-1 domain-containing 7A (THSD7A).

Anti-PLA2R autoantibodies can also be detected in blood. The presence of anti-PLA2R autoantibodies helps to differentiate primary membranous nephropathy from other causes of nephrotic syndrome when a biopsy is not possible. Anti-PLA2R antibody levels can be used to monitor response to therapy. A change in antibody level usually precedes a change in clinical status. Antibody levels have been shown to correlate with disease activity and risk of recurrence after kidney transplantation.

Reference range is a negative result. Specimen requirement is a red top tube of blood.

Beck L, Bonegio R, Lambeau G, et al: M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009;361:11-21

2. Schlumberger W, Hornig N, Lange S, et al: Differential diagnosis of membranous nephropathy with autoantibodies to phospholipase A2 receptor 1. Autoimmun Rev 2014 Feb;13(2)108-113

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