Phospholipase A2 Antibody (PLA2R) Antiphospholipase A2 Antibody MPLA2R

Immunology

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Description

Membranous glomerulonephritis presents with nephrotic syndrome or proteinuria and is identified on renal biopsy by epithelial IgG and C3 deposition. The disease is more common in males than females (2:1) and has a peak incidence between 40 and 50 years of age. Membranous nephropathy can be classified as either primary (idiopathic), which occurs in 75% of cases, or secondary. Secondary membranous is associated with malignancy, autoimmunity, infection and drugs. Primary membranous may have an autoimmune component with about 70% cases showing antibodies to M type phospholipase A2 receptor (1). Phospholipase A2 receptors are transmembrane glycoproteins (MW 185 KDa) found in the lungs, placenta, leukocytes and also expressed on podocytes in the kidney. Binding of antibody to PLA2R could cause subepithelial immune complex deposition and complement activation which then results in proteinuria and nephrotic syndrome (2). One third of primary membranous cases will develop end stage renal disease, one third will have a persistent proteinuria and one third will have spontaneous remission. APLA2R antibodies are lower in patients in partial or complete remission compared to those with active disease and increasing quantitation (3,4,5). Spontaneous remission also occurs less frequently in patients with high antibody values (6). APLA2R antibodies have also been shown to be markers for monitoring the patients response to immune suppression and can fall to normal range values 3-6 months before there are signs of clinical remission (5,7). Patients with membranous nephropathy undergoing renal transplantation have a disease recurrence of up to 45% (8) but using APLA2R antibody levels to identify these individuals has not given conclusive results (7,9). APLA2R antibodies have been described in patients with secondary membranous nephritis although it is suggested that these individuals also had concurrent primary membranous nephritis(10). APLA2R antibody measurement may have a role in identifying primary from secondary membranous nephropathy and also in disease monitoring. However they should not be viewed as a replacemant for renal biopsy in the investigation of patients presenting with nephrotic syndrome (11).

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Indications

Primary (idiopathic) membranous nephropathy.

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Sample Type

2mL Serum (Gel 5mL Yellow tube). Requests from outside Sheffield: Transport at ambient temperature via Royal Mail or Courier.

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Reference Range

<14 RU/mL = Negative.
14 - 20 RU/mL = Borderline.
>20 RU/mL = Positive.

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Turnaround Time

Within 2 weeks

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Testing Frequency

Weekly

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References

Bech L, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. 2009. N Eng J Med. 361: 11-21. [Ref 1].Ronco P, Cebiec H. Antigen identification in membranous nephropathy moves towards targeted monitoring and new therapy. J Am Soc Nephrol. 2010. 21: 564-569. [Ref 2].Kaningicherla D, et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. 2013. Kidney Int. 83: 940-948. [Ref 3].Hofstra JM, et al. Anti-phospholipase A�� receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2011. 6: 1286-1291. [Ref 4].Beck LH, Salant DJ. Membranous nephropathy: recent travels and new roads ahead. Kidney Int. 2010. 77:765-770. [Ref 5].Hofstra Jm, et al. Anti-phospholipase A2 receptor antibody titre and subclass in idiopathic membranous nephropathy. J Am Soc nephrol. 2012. 23: 1735-1743. [Ref 6].Stahl R, Hoxha E, Fechner K. PLA2R autoantibodies and recurrent membranous nephropathy after transplant. N Eng J Med. 2010. 363:496-498. [Ref 7].Choy BY, Chan TM, Lai KN. Recurrent glomerulonephritis after kidney transplantation. Am J Transplant. 2006. 6(11): 2535-2542. [Ref 8].Debiec H, Martin L, Jouanneau C, et al. Autoantibodies specific for the phospholipase A2 receptor in recurrent and De Novo membranous nephropathy. Am J Transplant. 2011. 11(10): 2144-2152. [Ref 9].Qin W, Beck LH, Zeng C, et al. Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol. 2011. 22(6): 1137-1143. [Ref 10].Hofstra JM, Wetzels JF. Anti PLA2R antibodies in membranous nephropathy: Ready for routine clinical practice? Neth J Med. 2012. 70:109-113. [Ref 11].

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See Also

Renal Biopsy.

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