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Abstract: SA-PO342

PLA2R1 Epitope Recognition Patterns and Clinical Outcome in Patients with Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Hoxha, Elion, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany
  • Zahner, Gunther, University hospital hamburg, Hamburg, Germany
  • Reinhard, Linda, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany
  • Stahl, Rolf A., University of Hamburg, Hamburg, Germany
Background


Phospholipase A2 receptor 1 antibodies (PLA2R1-ab) are found in 80% of patients with membranous nephropathy (MN). While PLA2R1-ab levels are closely associated with treatment response and disease prognosis, the clinical role of epitope regions targeted by autoantibodies is less clear.

Methods


The epitope recognition patterns of PLA2R1-ab from 150 patients with newly diagnosed PLA2R1-associated MN were analyzed by Western blot and correlated with disease activity, clinical characteristics and outcome.

Results


In addition to the three known epitope regions in the CysR, CTLD1 and CTLD7 domains, we identified a fourth epitope region in the CTLD8 domain of PLA2R1. While PLA2R1-ab from all patients recognized an epitope in the N-terminal region (defined as CysR – CTLD1 domains), 82.7% of patients also recognized a C-terminal epitope in PLA2R1, namely in the CTLD7 and/or CTLD8 domain. Patients with C-terminal epitope recognition had almost 10-fold higher PLA2R1-ab levels, higher proteinuria and needed immunosuppressive treatment twice as often as patients with epitope recognition confined at the N-terminal region of PLA2R1. After adjusting for these factors in multivariate analyses, C-terminal epitope recognition was not predictive for any of the clinical study endpoints, defined as depletion of PLA2R1-ab, remission of proteinuria, and doubling of serum creatinine during follow-up. Additional dilution of sera recognizing C-terminal epitopes of PLA2R1 led to abolishment of C-terminal epitope recognition, while N-terminal epitopes remained detectable. Therefore, one can speculate, that some of the 17.3% of patients in our cohort, who only showed reactivity to the N-terminal region of PLA2R1, may also have had autoantibodies targeting the C-terminal region, however, the sensitivity of the method was not sufficient to detect them.

Conclusion


There are at least four target epitope regions in the PLA2R1 and a clear association between epitope recognition patterns and PLA2R1-ab levels. C-terminal epitope recognition is not associated with disease outcome if all other clinical variables are adjusted for, therefore considering PLA2R1-ab levels is fundamental for the interpretation of the clinical relevance of PLA2R1 epitope recognition patterns.

Funding

  • Private Foundation Support