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Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy
Peter D Burbelo1, Megha Joshi2, Adrija Chaturvedi1
1Dental Clinical Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland.
Background:
Circulating serum autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) are a key biomarker in the diagnosis and monitoring of primary membranous nephropathy (MN). However, little is known about the appearance and trajectory of PLA2R-AB before the clinical diagnosis of MN.
Methods:
Using the Department of Defense Serum Repository, we analyzed PLA2R-AB in multiple, 1054 longitudinal serum samples collected before diagnosis of MN from 134 individuals with primary MN, 35 individuals with secondary MN, and 134 healthy volunteers. We evaluated the presence and timing of non-nephrotic range proteinuria (NNRP) and serum albumin measurements in relation to PLA2R-AB status.
Results:
Analysis of PLA2R-AB in longitudinal serum samples revealed seropositivity in 44% (59 out of 134) of primary MN cases, 3% (one out of 35) of secondary MN cases, and in 0% of healthy controls. Among patients with MN, PLA2R-AB were detectable at a median of 274 days before renal biopsy diagnosis (interquartile range, 71-821 days). Approximately one third of the participants became seropositive within 3 months of MN diagnosis. Of the 21 individuals with documented prediagnostic NNRP, 43% (nine out of 21) were seropositive before NNRP was first documented and 28.5% (six out of 21) were seropositive at the same time as NNRP; 66% (39 out of 59) of those seropositive for PLA2R-AB had hypoalbuminemia present at the time antibody was initially detected. Twelve participants (20%) were seropositive before hypoalbuminemia became apparent, and eight participants (14%) were seropositive after hypoalbuminemia became apparent.
Conclusions:
Circulating PLA2R-AB are detectable months to years before documented NNRP and biopsy-proven diagnosis in patients with MN.
Insights
Autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) can be detected months before membranous nephropathy (MN) diagnosis. This finding aids in understanding the early trajectory of PLA2R-AB in MN patients.
Area of Science:
- Nephrology
- Immunology
- Clinical Biomarkers
Background:
- Autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) are crucial for diagnosing and monitoring primary membranous nephropathy (MN).
- The early appearance and progression of PLA2R-AB before clinical diagnosis of MN remain largely uncharacterized.
Purpose of the Study:
- To investigate the presence and timing of PLA2R-AB in relation to clinical diagnosis in patients with primary and secondary MN.
- To evaluate the association of PLA2R-AB with non-nephrotic range proteinuria (NNRP) and hypoalbuminemia before diagnosis.
Main Methods:
- Analysis of 1054 longitudinal serum samples from 134 primary MN, 35 secondary MN, and 134 healthy individuals using the Department of Defense Serum Repository.
- Assessment of PLA2R-AB seropositivity, timing of detection relative to diagnosis, and correlation with NNRP and serum albumin levels.
Main Results:
- PLA2R-AB seropositivity was found in 44% of primary MN cases, 3% of secondary MN cases, and 0% of controls.
- In primary MN patients, PLA2R-AB was detectable a median of 274 days before biopsy.
- A significant proportion of patients showed detectable PLA2R-AB before or concurrent with non-nephrotic range proteinuria and hypoalbuminemia.
Conclusions:
- Circulating PLA2R-AB are detectable months to years prior to the onset of non-nephrotic range proteinuria and biopsy-proven diagnosis in patients with MN.
- These findings highlight the potential of PLA2R-AB as an early diagnostic marker for MN.
