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Abstract: TH-OR25

Exploring Epitope Spreading of PLA2R and Its Clinical Relevance in Idiopathic Membranous Nephropathy (IMN) Based on Yeast Surface Display System

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Liu, Yanan, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
  • Chen, Peng, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
  • Hong, Junxian, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
  • Qin, Yan, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
Background

PLA2R is the main target antigen of idiopathic membranous nephropathy (IMN). The PLA2R extracellular segment consists of Ricin, FNII and 8 CTLDs. The major epitope is located in Ricin, and CTLD1, CTLD7 and CTLD8 have also been found as epitopes. The presence of epitope spreading and its clinical significance are controversial.

Methods

A random library of PLA2R was constructed by yeast surface display technique and screened by serum from 18 patients with PLA2R-associated IMN. Serum was prospectively collected from 389 patients. A batch flow analysis was carried out with the monoclonal yeast of each epitope. The clinical value of epitope was explored. The dynamic changes of epitope profiles during follow-up were observed.

Results

1. The first PLA2R yeast surface display system was constructed.
2. In addition to Ricin, CTLD1, CTLD7, and CTLD8, 3 new epitopes (CTLD4, CTLD5, and CTLD6) were found (Figure 1).
3. The positive rates of CTLD1 and CTLD7 were about 50%. CTLD6, CTLD8 and CTLD4 were weak epitopes with a positive rate of less than 10%. 69 (17.7%) patients had epitope limited to Ricin.
4. 24hUP increased with the number of epitopes. The relationship between epitope spreading and 24hUP in subgroup divided by anti-PLA2R titer was consistent with the whole cohort.
5. By multivariate COX regression, gender, age, baseline 24hUP, anti-PLA2R titer were adjusted. Patients with epitope number ≥4 had lower response rates than patients with only 1 epitope (HR 0.571, 95%CI 0.363-0.899, p=0.015).
6. Reversal of epitope spreading was observed in responders. Further epitope spreading was observed in non-responders.

Conclusion

We identified 3 new epitopes through PLA2R yeast surface display system. Epitope spreading in PLA2R was confirmed. The epitope number was correlated with 24hUP. Baseline epitope spreading had a prognostic value for remission independent of anti-PLA2R Ab titer and 24hUP. Clinical remission was accompanied with epitope reversal.

Funding

  • Clinical Revenue Support