Anti–Phospholipase A2 Receptor (PLA2R) Antibodies

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults worldwide. Although it occurs predominantly in Caucasian men over 40 years of age, it can affect both sexes and all ethnic groups. The clinical course is variable: in most cases it regresses spontaneously or remains stable; in about one third of cases it worsens, progressing to chronic kidney failure with a risk of end-stage renal disease. In approximately 20% of patients, MN is secondary. For therapeutic purposes, secondary MN must be distinguished from primary (idiopathic) MN (pMN).

The autoimmune mechanisms underlying pMN involve the formation of autoantibodies against the antigens PLA2R and thrombospondin type I domain-containing 7A (THSD7A). These transmembrane proteins are expressed on podocyte surfaces in human glomeruli. When autoantibodies bind, podocytes are damaged and proteins pass into the primary urine. As proteinuria increases, the long-term risk of kidney failure rises, with high morbidity and mortality – particularly due to thromboembolic and cardiovascular complications.

Diagnosis of pMN is performed by kidney biopsy with histology and/or electron microscopy. Serological detection of pMN-specific antibodies is faster and less burdensome for the patient.

PLA2R has been defined as the principal target antigen in pMN; anti-PLA2R antibodies are highly specific and are detected in up to ~75% of affected patients.

Antibody levels also correlate with disease course and prognosis in pMN. Likewise, treatment success, clinical remission, or relapse can be monitored by tracking antibody titres.