Abstract: FR-PO864
Circulating Antibodies to Recombinant Exostosin 1 Are Detected in Patients with Primary and Secondary Membranous Nephropathy
Session Information
- Glomerular Diseases: Membranous Nephropathy, SLE, Complement
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Caster, Dawn J., University of Louiville, Louisville, Kentucky, United States
- Tandon, Shweta, University of Louiville, Louisville, Kentucky, United States
- McLeish, Kenneth R., University of Louisville, Louisville, Kentucky, United States
- Powell, David W., University of Louisville, Louisville, Kentucky, United States
Background
Antibodies to phospholipase A2 receptor (PLA2R), a transmembrane podocyte protein, account for approximately 70% of cases of primary membranous nephropathy (MN). Antibodies to thrombospondin type-1 domain-containing 7A (THSD7A) account for approximately 10% of anti-PLA2R negative patients. Anti-PLA2R and anti-THSD7A are rarely found in secondary MN, including class V lupus nephritis (LN). A recent report by Sethi and colleagues demonstrated glomerular deposition of exostosin 1/exostosin 2 (EXT1/EXT2) in about 10% of patients with anti-PLA2R negative MN, including 8 of 18 patients with pure class V LN. However, anti-exostosin antibodies were not detected in the 7 patients tested. This study tested the hypothesis that patients with class V LN have circulating antibodies to exostosin 1 (EXT1).
Methods
Recombinant full length human EXT1 (Abnova) was separated by SDS-PAGE and transferred onto a nitrocellulose membrane. Membranes were incubated overnight at 4°C with sera from patients (1:50-1:100) or rabbit polyclonal antibody to EXT1 (ABclonal; dilution 1:1000) followed by appropriate HRP conjugated secondary antibodies. 5 patients with class V LN (4 pure class V, 1 with class III/V) and 4 patients with primary MN (3 anti-PLA2R+) were evaluated. Secondary antibody controls were negative. All blots were run twice for validation.
Results
We found 3 of 5 patients with class V LN (including 1 patient with class III/V LN) had circulating antibodies to EXT1. We found 2 of 4 patients with primary MN (both anti-PLA2R+) had circulating antibodies to EXT1.
Conclusion
We conclude that circulating antibodies to EXT1 are found in patients with primary and secondary membranous nephropathy, including patients with circulating anti-PLA2R.
Funding
- NIDDK Support