Abstract: PO1590
Reduction of Urinary Levels of Lectin Pathway Complement Components in an IgA Vasculitis Patient After MASP-2 Inhibition with Narsoplimab
Session Information
- Glomerular Diseases: Clinicopathological Features and Outcomes in IgAN, Lupus Nephritis, and Vasculitis
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Pérez Alós, Laura, Rigshospitalet, Copenhagen, Denmark
- Scionti, Katrin, University of Leicester, Leicester, United Kingdom
- Molyneux, Karen, University of Leicester, Leicester, United Kingdom
- Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
- Garred, Peter, Rigshospitalet, Copenhagen, Denmark
Background
A young female suffering from IgA vasculitis was treated with 4 mg/kg weekly infusions of narsoplimab (a MASP-2 inhibitor) for 12 weeks. MASP-2 is considered the key activator of the lectin pathway (LP) by cleaving C4 and C2, after the binding of LP pattern recognition molecules to its ligands. Inhibition of MASP-2 is predicted to decrease complement activation in complement-mediated kidney diseases. In this exploratory study we measured the levels of different LP complement components to evaluate the influence of narsoplimab on complement activation.
Methods
Urine levels of complement activation markers (C4c, C3bc and soluble C5b-9) and serum and urine levels of ficolin-1, -2 and -3, MBL, CL-11, MASP-3, MAP-1 and PTX-3 were measured using sandwich-ELISAs. Urine samples were subjected to LC/MS-MS. Correlations between LC/MS-MS and sandwich-ELISA were conducted using simple linear regression and Spearman’s rank correlation coefficient. Significance: p value < 0.05. Urine proteins were adjusted for creatinine excretion and expressed as specific protein/creatinine ratio.
Results
C4c/creatinine ratio, ficolin-3/creatinine ratio and C3bc/creatinine ratio levels were decreased 75%, 58% and 29%, respectively, from baseline to the end of the treatment; while levels of MBL and CL-11 remained stable during the treatment. C4c/creatinine ratio levels were significantly correlated to LC/MS-MS C4 data (R2: 0.5059; Spearman r: -0.5824, p=0.0402). Circulating levels of complement components in serum were unaltered during treatment. Soluble C5b-9, ficolin-1, -2, MASP-3 and MAP-1 were undetectable in urine and PTX-3 was undetectable in both urine and serum.
Conclusion
This is the first report describing the effect of narsoplimab on urinary complement levels in a complement-mediated kidney disease. Our data suggest a decrease in local complement activation with narsoplimab treatment. Further studies are ongoing to evaluate the use of urine as a non-invasive, inexpensive and readily accessible resource to monitor responses to complement-directed treatments.
Funding
- Commercial Support –