Abstract: SA-PO715
In Situ Visualization of C3/C5 Convertases: A New Diagnostic Tool to Differentiate Complement Activation in Kidney Biopsies
Session Information
- Pathology and Lab Medicine: Clinical
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1602 Pathology and Lab Medicine: Clinical
Authors
- Wiech, Thorsten, Department of Pathology, University Hospital Hamburg Eppendorf, Hamburg, Germany
- Person, Fermin, University Hospital Basel, Basel, Switzerland
- Wulf, Sonia, UKE, Hamburg, Germany
- Buescheck, Franziska, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Hamburg, Germany
- Biniaminov, Sergey, HS Analysis, Karlsruhe, Germany
- Fehrle, Wilfrid, UKE, Hamburg, Germany
- Oh, Jun, University Childrens Hospital, Hamburg, Germany
- Skerka, Christine, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
- Zipfel, Peter F., Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
Background
Deregulated complement activation contributes to or drives the pathogenesis of various kidney diseases. Currently, the diagnosis of complement activation in kidney diseases is primarily based on detection of complement activation products in glomerular tissue and of consumption of complement components or generation of split products in plasma. Up to now a method to directly identify, localize and differentiate complement convertases in tissue has been lacking.
Methods
We established a new in situ method for the detection of the assembled C3/C5-Convertases of the classical/lectin and alternative pathways using the bright field proximity ligation assay. We compared kidney biopsies derived from cases of systemic lupus nephritis (SLE, n=10) with cases of thrombotic microangiopathy (TMA, n=9) due to atypical hemolytic syndrome, using zero hour transplant biopsies as normal controls (n=5).
Results
As expected, SLE cases revealed a higher density of classical pathway C3/C5 convertases, while TMA cases showed less classical pathway enzymes and a higher density of alternative pathway C3/C5 convertase signals.
Conclusion
We introduce the first methodological workflow for the visualization, differentiation and quantification of classical/lectin and alternative C3/C5 convertases directly within the tissue specimen.