Table 3.

Clinical and translational correlates of circulating levels of anti-PLA2R^a

70%–80% of patients with PMN have anti-PLA2R/THSD7A antibody (4–6,11)
Anti-PLA2R antibody is about 80% sensitive and 100% specific for PMN (although rare patients with sarcoid, HBV, HCV, HIV, and cancer have been reported) (4,7,8,20,22)
Anti-PLA2R antibody can be present for many months before proteinuria appears (22,26)
In non-nephrotic patients, low, or declining, anti-PLA2R levels predict spontaneous remission and high levels predict progression to nephrotic syndrome (47,48,51)
Anti-PLA2R–negative patients can become positive later (4,47,48)
High antibody levels (before and after treatment) correlate with proteinuria, response to therapy, and (after therapy) long-term outcomes (4–8,50,51,70,71)
Patients with higher antibody levels require more prolonged immunosuppression to achieve remission rates comparable to those with lower levels (63,70)
Expansion of the specificity of anti-PLA2R antibody to include additional epitopes (epitope spreading) correlates with a worse prognosis (36)
Patients with IgG4 antibody directed only at the cysteine-rich epitope of PLA2R have a higher rate of spontaneous remission (36)
Anti-PLA2R levels go down in remission and return with relapse (4–8,47,48)
Elevated anti-PLA2R levels after treatment predict relapse (5–8,47,48)
Elevated anti-PLA2R levels at the time of transplantation predict recurrence (especially if DQA1a05:01/05 positive) (71,83–85)
Disappearance of anti-PLA2R antibodies (immunologic remission) precedes renal remission (disappearance of proteinuria) by weeks to months (5–8)
Patients previously positive for anti-PLA2R/THSD7A who become negative will exhibit positive glomerular staining for weeks to months (5–8,13,20,21)
>50% of cases of pediatric PMN are PLA2R-positive (3)

PMN, primary membranous nephropathy; HBV, hepatitis B; HCV, hepatitis C.

^aAlthough established in only a few cases, most of these associations are likely similar in anti-THSDA–mediated PMN.