PLAIR is Associated with Membranous Nephropathy
Phospholipase A2 Receptor (PLA2R) is definitively associated with membranous nephropathy (MN), making option B the correct answer. 1
Understanding PLA2R and Membranous Nephropathy
PLA2R is a key biomarker in membranous nephropathy, serving as both a diagnostic indicator and a target for monitoring disease activity. The relationship between PLA2R and membranous nephropathy has been well-established in recent clinical guidelines:
- PLA2R antibodies are highly specific for primary membranous nephropathy
- According to KDIGO 2021 guidelines, a positive anti-PLA2R antibody test in a patient with nephrotic syndrome is sufficient to diagnose membranous nephropathy even without kidney biopsy 1
- PLA2R antibody levels can be used to monitor treatment response and guide therapy adjustments 1
Diagnostic Significance
The diagnostic value of PLA2R testing is so significant that recent guidelines have changed the diagnostic approach to membranous nephropathy:
- A kidney biopsy is no longer required to confirm MN in patients with nephrotic syndrome and positive anti-PLA2R antibodies 1
- PLA2R staining in kidney biopsy samples can identify membranous nephropathy even in patients who are seronegative for circulating antibodies 1
- Approximately 52% of patients with primary membranous nephropathy test positive for PLA2R antibodies 2
Clinical Implications
The identification of PLA2R has revolutionized the management of membranous nephropathy:
- PLA2R antibody levels can be monitored every 3-6 months during treatment 1
- Disappearance of anti-PLA2R antibodies typically precedes clinical remission 1
- Rising antibody levels may predict disease relapse and guide preemptive therapy 3
Important Caveats
While PLA2R is strongly associated with primary membranous nephropathy, there are important considerations:
- PLA2R positivity does not completely rule out secondary causes of membranous nephropathy
- Secondary causes should still be evaluated, including malignancy, infections, and autoimmune diseases 1
- Some cases of secondary membranous nephropathy, including those associated with sarcoidosis 4 and possibly lymphoma 5, can also show PLA2R positivity
- A subset of PLA2R-associated MN patients may have circulating antibodies but negative staining on kidney biopsy, which may represent a more severe disease phenotype 6
Differential Diagnosis
It's important to distinguish membranous nephropathy from other glomerular diseases:
- Minimal change disease (option A) is not associated with PLA2R antibodies
- Goodpasture's syndrome (option C) is associated with anti-GBM antibodies, not PLA2R 1
- While some cases of anti-GBM disease can be associated with monoclonal gammopathy, this is distinct from the PLA2R-associated membranous nephropathy 1
The evidence clearly demonstrates that PLA2R is specifically associated with membranous nephropathy, making option B the correct answer.