Abstract: PO1811
Nephritic Factor Function Over Time
Session Information
- Glomerular Diseases: IgA, C3G, and FSGS
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Culek, Christopher, Molecular Otolaryngology and Renal Research Laboratories, Iowa City, Iowa, United States
- Hall, Monica D., Molecular Otolaryngology and Renal Research Laboratories, Iowa City, Iowa, United States
- Zhang, Yuzhou, Molecular Otolaryngology and Renal Research Laboratories, Iowa City, Iowa, United States
- Smith, Richard J., Molecular Otolaryngology and Renal Research Laboratories, Iowa City, Iowa, United States
- Nester, Carla Marie, Molecular Otolaryngology and Renal Research Laboratories, Iowa City, Iowa, United States
Background
Nephritic factors (Nef) are autoantibodies that stabilize and dysregulate the function of the C3 convertase, the cornerstone of complement amplification. Their association with renal inflammation central to the C3 Glomerulopathies (C3G) is well reported, however it is unknown whether Nefs 1) change over time, 2) correlate with serologic biomarker assessments, and/or 3) are useful for predicting risk for relapse of C3G. We aimed to create a novel assay that allows comparison of Nef properties over time. We further sought to correlate these results with an array of serologic biomarkers. We hypothesized that when Nef activity remains high, this abnormality is associated with ongoing serologic biomarker abnormalities.
Methods
The test subject was a C3G patient with disease recurrence 7 months after renal transplant. Reagent C3 convertase was formed by injecting factor B, factor D, and patient-derived IgG (versus normal pooled human IgG as a control) over a C3b-immobilized CM5 chip (Biacore X100) followed by injection of Decay Accelerating Factor (DAF) to remove unstabilized convertase. Nef-stabilized convertases were allowed to dissociate for 3600 minutes. Kinetic data were collected at five time points during dissociation. Data for each clinical time point were normalized to the amount of stabilized convertase at t=0. Serologic biomarker assays were performed as previously described.
Results
Qualitatively, test subject Nef stabilized the convertase 1.32 to 1.44 fold longer than unstabilized convertase. Between sample time point variability at 800s was less than 13%. Nef function correlated with serologic biomarker abnormalities at all 4 samples.
Conclusion
Using a novel assay, we show that Nefs isolated from a test subject remained remarkably stable over a 28-month period. In addition, the stabilizing effect of Nefs on C3 convertase consistently correlated with serologic biomarker abnormalities. We are extending this approach to additional C3G patients with and without recurrence of disease in transplant in order to provide a method for comparing Nefs over time, thereby defining the role of Nef-stabilizing function as an at-risk biomarker for C3G recurrence in transplant.
Funding
- NIDDK Support