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Abstract: SA-PO955

A Multi-Targeted Serologic Approach for Antigen-Specific Diagnosis of Membranous Nephropathy (MN) in the Clinical Routine

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Reinhard, Linda, III. Deparment of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • Brauer, Céline Marie, III. Deparment of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • Wiech, Thorsten, Institute for Pathology, Section Nephropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • Hoxha, Elion, III. Deparment of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany
Background

MN is caused by circulating antibodies (ab) targeting PLA2R1 or THSD7A in 70-80% of cases. Over the last years a diverse repertoire of other potential antigens has been identified, however, it remains unclear how an autoantibody-specific diagnostic workflow in patients with MN can be implemented in clinical routine.

Methods

We implemented a multi-targeted serologic screening procedure, which allows detection of ab directed against sensitive, conformational epitopes of multiple antigens within one experiment. Results were validated using ELISA, Western blot and immunohistochemistry of kidney biopsies. The clinical applicability of this system was tested in 410 patients with biopsy-proven MN.

Results

A PLA2R1-induced MN was diagnosed in 307 (74.9%) of 410 patients. Using our multi-targeted serology screening approach, we identified 17 (4.2%) NELL1-ab positive patients, 10 (2.4%) THSD7A-ab positive patients and 12 (2.9%) patients with circulating ab against one of the other antigens (PCDH7, HTRA1, NTNG1, CNTN1, or SEMA3B). Interestingly, 5 of these 12 patients showed ab against two different antigens simultaneously. Every ab result was validated using Western Blot showing concordance of results in 95% of cases.
20 (31.2%) of the remaining 64 sera showed reactivity to different preparations of human glomerular extract (HGE), indicating that for each antigen, ab detectability is strongly dependent on the experimental protocols used to extract the HGE antigens. 83% of patients with no reactivity to any antigen or the HGE in any experimental condition, had a remission of proteinuria, in 66% of them it was a spontaneous remission without use of immunosuppression.

Conclusion

We report a multi-targeted serologic approach, which allows an antigen-specific diagnosis of MN within days and is therefore applicable in clinical routine. To fully accomplish an antigen-specific MN diagnosis in every patient, sera with reactivity to HGE are used for antigen identification via immunoprecipitation. The 10% of cases with no serologic activity show a good prognosis, while antigen identification is performed by tissue-based mass spectrometry. For the implementation of the later two steps into clinical routine further adjustments are required, especially concerning the turn-around time for antigen identification.

Funding

  • Government Support – Non-U.S.