Kidney Week

Abstract: SA-PO342

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

Session Information

• Glomerular Diseases: Immunology and Inflammation - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

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

Elion Hoxha,

• Zahner, Gunther, University hospital hamburg, Hamburg, Germany

Gunther Zahner,

• Reinhard, Linda, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany

Linda Reinhard,

• Stahl, Rolf A., University of Hamburg, Hamburg, Germany

Rolf A. Stahl,

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