Phospholipase Receptor A2 Antibody
In the United States, nearly one third of cases of the nephrotic syndrome are attributed to membranous nephropathy. In 25% of cases of membranous nephropathy, the disease occurs secondary to a medication or another disease such as systemic lupus erythematosis, hepatitis B virus or hepatitis C virus infection, syphilis, thyroiditis, or cancer. The remaining cases are considered to be primary. Primary and secondary membranous nephropathies are clinically indistinguishable. Both are characterized by a gradual progression to the nephrotic syndrome over a period of months, often with preserved renal function and normal blood pressure.
The primary 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 M-type phospholipase A2 receptor, which is a transmembrane protein in glomerular podocytes. Autoantibodies are predominantly of the IgG4 subclass. Because these autoantibodies are not detected in secondary causes of membranous nephropathy 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 podocyte antigen, thrombospondin type-1 domain-containing 7A (THSD7A).
Anti-PLA2R autoantibodies can also be detected in blood. Serologic testing for anti-PLA2R antibodies has become a key component of the diagnostic workup for membranous nephropathy because it is less invasive than biopsy and has very high specificity (99%). A positive serologic test may obviate the need for a kidney biopsy in many patients. The sensitivity of serologic testing for anti-PLA2R antibodies (78%) is not sufficiently high for a negative test to completely rule out the diagnosis of PLA2R type of membranous nephropathy.
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.
Detection of anti-PLA2R IgG antibodies by ELISA is commonly performed using an assay manufactured by Euroimmun. Reference range is a negative result. Specimen requirement is a red top tube of blood.
References
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
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
Morris CA et al. Case 17-2018: A 40-Year-Old Woman with Leg Swelling and Abdominal Distention and Pain. N Engl J Med 2018;378:2124-32.
