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Abstract: TH-PO1010

Novel ELISA for THSD7A Autoantibodies in Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Zaghrini, Christelle, Institut de Pharmacologie Moleculaire et Cellulaire, University Cote d'Azur , Sophia Antipolis, France
  • Seitz-Polski, Barbara, Pasteur University Hospital, Nice, France
  • Justino, Joana, Institut de Pharmacologie Moleculaire et Cellulaire, University Cote d'Azur , Sophia Antipolis, France
  • Dolla, Guillaume, Institut de Pharmacologie Moleculaire et Cellulaire, University Cote d'Azur , Sophia Antipolis, France
  • Payre, Christine, Institut de Pharmacologie Moleculaire et Cellulaire, University Cote d'Azur , Sophia Antipolis, France
  • Jourde-Chiche, Noemie, Aix-Marseille University, Marseille, France
  • van de Logt, Anne-Els, Radboud University Medical Center, Nijmegen, Netherlands
  • Lonnbro-Widgren, Jennie, Sahlgrenska University Hospital, Gothenburg, Sweden
  • Nystrom, Jenny C., University of Gothenburg, Goteborg, Sweden
  • Cui, Zhao, Peking University First Hospital, Peking, China
  • Wetzels, Jack F., Radboud University Medical Center, Nijmegen, Netherlands
  • Ghiggeri, Gian Marco, G. Gaslini Children Hospital, Genoa, Italy
  • Beck, Laurence H., Boston University Medical Center, Boston, Massachusetts, United States
  • Ronco, Pierre M., Hospital Tenon, Sorbonne University , Paris, France
  • Debiec, Hanna, Hospital Tenon, Sorbonne University , Paris, France
  • Lambeau, Gerard J., Institut de Pharmacologie Moleculaire et Cellulaire, University Cote d'Azur , Sophia Antipolis, France
Background

In 2014, THSD7A was identified as a second autoantigen for 2-5% of membranous nephropathy (MN) patients whereas PLA2R1 is the major autoantigen for 70% of patients. Detection and accurate measurement of anti-PLA2R1 and anti-THSD7A titers provide key biomarkers to diagnose MN, monitor disease activity and predict clinical outcome. To date, antibodies in THSD7A-associated MN patients are only evaluated semi-quantitatively by WB and IIFT. We aimed to develop a robust and rapid assay for the quantitative measurement of antibody levels in THSD7A-associated MN patients.

Methods

Screening of 1012 biopsy-proven MN patients led to the identification of 28 THSD7A-positive patients by ELISA. Screening of additional MN patients, mostly PLA2R1-negative, identified 21 more cases, establishing the largest cohort of 49 THSD7A-positive patients to date. We validated the positivity of the 49 patients by ELISA, WB, IIFT and biopsy staining. We analyzed the clinical parameters of this population for age, gender, disease activity and possible links to etiology including malignancy. We described eight patients double positive for THSD7A and PLA2R1 antibodies.

Results

The novel ELISA and commercial IIFT titers correlated significantly (p<0.0001). Among the 49 patients with anti-THSD7A antibodies, 57% were males. Females were younger than males (49 versus 67 years, p=0.003). Levels of anti-THSD7A antibodies were similar between male and female patients and correlated with disease activity and treatment efficacy. The double positive patients had varying antibody titers for both antigens and displayed no clinical difference compared to the rest of the population. Patients with a history of malignancy (16%) were older than others (76 versus 54 years old, p=0.002) and only 3 were diagnosed for malignancy within 2 years of MN diagnosis.

Conclusion

This novel ELISA assay can be used to identify patients with THSD7A-associated MN and monitor antibodies during follow-up. Our data suggest a weak association between MN and malignancy in our population of THSD7A-positive patients.

Funding

  • Government Support - Non-U.S.