Monitoring Ravulizumab effect on complement assays
| Autor: | Meera Sridharan, Ronald S. Go, Paula M. Ladwig, Mark A Martinez, Maria Alice V. Willrich, David L. Murray |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.drug_class Immunology Receptors Fc Pharmacology Antibodies Monoclonal Humanized Monoclonal antibody 03 medical and health sciences Classical complement pathway 0302 clinical medicine Monitoring Immunologic medicine Humans Immunology and Allergy Complement Pathway Classical Precision Medicine Atypical Hemolytic Uremic Syndrome Immunoassay Liposome medicine.diagnostic_test Chemistry Histocompatibility Antigens Class I Complement C5 Eculizumab Blockade Complement (complexity) Complement Inactivating Agents 030104 developmental biology Therapeutic drug monitoring Liposomes Alternative complement pathway 030215 immunology medicine.drug |
| Zdroj: | Journal of Immunological Methods. 490:112944 |
| ISSN: | 0022-1759 |
| DOI: | 10.1016/j.jim.2020.112944 |
| Popis: | Ravulizumab is a new C5 inhibitor therapeutic monoclonal antibody with a longer half-life than eculizumab. Monitoring complete complement blockade by eculizumab has allowed personalized therapy in specific settings. Similar action is expected with ravulizumab. Ravulizumab has 4 different amino acids from eculizumab, which allow greater affinity for the FcRn immunoglobulin receptor and change the affinity of the molecule for C5. Here we investigate if clinical lab tests traditionally used to monitor complement blockade for eculizumab are appropriate for monitoring complement blockade caused by ravulizumab. De-identified serum samples with known normal complement activity were spiked with increasing amounts of ravulizumab, from zero to 1000 μg/mL. Measurement of classical pathway function (CH50) and C5 function using a liposome method (Wako Diagnostics) showed >50% complement inhibition starting with 50 μg/mL of ravulizumab, but inhibition >95% of complement activity was not achieved, with residual measurements of 11% at 700 μg/mL. In contrast, measurement of alternative pathway function using an ELISA (AH50, Wieslab) showed alternative pathway function inhibition of 80% at 50 μg/mL of ravulizumab and > 95% at 200 μg/mL, which is consistent with expected therapeutic concentrations of ravulizumab >175 μg/mL. If replicated in patient sera, AH50 could be a suitable therapeutic monitoring tool. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect