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Abstract: SA-PO341

Pre-Diagnostic Evaluation of Anti-Phospholipase A2 Receptor Antibodies in Primary Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Joshi, Megha Raj, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
  • Burbelo, Peter D., NIDCR, NIH, Bethesda, Maryland, United States
  • Waldman, Meryl A., NIH, Bethesda, Maryland, United States
  • Gordon, Sarah M., TAMC, Kaneohe, Hawaii, United States
  • Thurlow, John Stephen, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
  • Olson, Stephen W., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
Background

M-type phospholipase A2 receptor antibodies (PLA2R –Ab) are present in 60-80% of primary membranous nephropathy (pMN) cases at diagnosis. PLA2R-Ab is assumed to directly contribute to pMN pathophysiology, but there has not been confirmatory animal models or evaluation of PLA2R –Ab before pMN diagnosis. We sought to describe PLA2R-Ab levels before both biopsy diagnosis and documented proteinuria before biopsy diagnosis to better understand pMN pathophysiology.

Methods

We performed a retrospective case-control Department of Defense Serum Repository (DoDSR) study comparing PLA2R-Ab in patients with pMN, presumed secondary MN, and healthy controls. MN cases were first identified and confirmed by review of the military electronic medical record. Background data was collected to include the earliest date of abnormal proteinuria and the most recent date of negative proteinuria before biopsy diagnosis. Based on background and biopsy data, MN patients were divided into pMN and secondary MN cases. The DoDSR then provided up to 4 prediagnostic specimens for each MN case and age, race, sex and age of serum matched healthy controls. PLA2R-Ab was measured at the NIH using a luciferase assay.

Results

More pMN cases had elevated PLA2R-Ab than secondary membranous disease controls before biopsy diagnosis [44% (59/134) vs. 2.8% (1/35), p<0.001]. No matching healthy controls had detectable PLA2R-Ab at any time point. PLA2R-Ab became elevated a median of 274 days prior to biopsy diagnosis (IQR: 63days, 811 days). 15 cases demonstrated significantly elevated prediagnostic PLA2R-Ab at or up to 5 years prior to the earliest documentation of non-nephrotic range proteinuria before biopsy diagnosis. Two unique cases demonstrated elevated PLA2R-Ab with confirmed negative proteinuria over a year before biopsy diagnosis.

Conclusion

PLA2R-Ab is detectable not only before biopsy proven pMN, but also prior to the earliest subclinical presence of non-nephrotic range proteinuria which supports a direct contribution to the pathogenesis of pMN. Early serum testing of PLA2R-Ab in patients with unexplained non-nephrotic range proteinuria may allow for early diagnosis and monitoring of pMN.

Funding

  • Other NIH Support