26516 Primary Membranous Nephropathy Diagnostic Cascade, Serum

​​Anti-PLA2R, PLA2R, Anti-THSD7A, Thrombospondin, THSD7​

​Distinguishing primary from secondary membranous nephropathy using an algorithmic approach

Monitoring patients with membranous nephropathy at very low antibody titers

Screening for anti-phospholipase a2 receptor antibodies

​Centrifuge and aliquot serum into plastic vial within 2 hours of collection

​This test should not be used as a stand-alone test but an adjunct to other clinical information. A diagnosis of primary or secondary membranous nephropathy (MN) should not be made on a single test result. The clinical symptoms, results on physical examination, and laboratory tests (eg, serological tests), when appropriate, should always be taken into account when considering the diagnosis of primary versus secondary MN.​

Absence of circulating anti-phospholipase A2 receptor autoantibodies does not rule out a diagnosis of primary MN.

​Membranous nephropathy (MN) is a rare disease in which immune complexes deposit at the glomerular basement membrane, causing damage to the filtration barrier, resulting in proteinuria. Recent studies have shown that in approximately 70% of patients with primary MN (pMN), the immune complexes consist of autoantibodies against the podocyte protein M-type phospholipase A2 receptor (PLA2R). There is also evidence that levels of anti-PLA2R autoantibodies correlate well with disease activity and progression. The presence of anti-PLA2R antibodies could also potentially be used to differentiate pMN from other causes of nephrotic syndrome if a biopsy is not possible. Among patients with chronic kidney disease awaiting kidney transplantation, higher levels of anti-PLA2R could predict those more likely to recur after transplantation.

Mayo Clinic Laboratory data suggest that there is a high-concordance between the enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay PLA2R results; however, the ELISA assay alone may be preferred for monitoring patients with membranous nephropathy over time for trends in anti-PLA2R antibody levels.

In the remaining 30% of patients with MN who are PLA2R-negative, anti-thrombospondin type-1 domain-containing 7A (THSD7A) was shown to have an approximate 10% prevalence (ie, about 3% of all primary MN patients). Mouse podocytes express THSD7A and introduction of anti-THSD7A autoantibodies induces MN in murine models. Mouse podocytes do not express PLA2R so exogenous administration of anti-PLA2R does not recapitulate MN in mice. Additionally, THSD7A has been described as a potential tumor antigen and, thus, it has been suggested that THSD7A-positive patients merit a thorough cancer screening.

​Therapy outcome can be monitored by measuring the anti-phospholipase A2 receptor (PLA2R) antibody titer. A titer increase, decrease, or disappearance generally precedes a change in clinical status. Thus, the determination of the antibody titer has a high predictive value with respect to clinical remission, relapse, or risk assessment after kidney transplantation.​

According to the manufacturer's package insert, the EUROIMMUN Anti-PLA2R indirect immunofluorescence assay (IFA) was positive in 77.1% of patients with biopsy proven primary membranous nephropathy (pMN). This corresponds well with published literature that approximately 70% of patients with pMN will have anti-PLA2R antibodies.