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Callegari, I; Schneider, M; Aebischer, V; Voortman, MM; Proschmann, U; Ziemssen, T; Lindberg, R; Fischer-Barnicol, B; Khalil, M; Kappos, L; Kuhle, J; Sanderson, NSR; Derfuss, T.
Natalizumab in cerebrospinal fluid and breastmilk of patients with multiple sclerosis.
Ther Adv Neurol Disord. 2023; 16: 17562864221150040
Doi: 10.1177/17562864221150040
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- Co-Autor*innen der Med Uni Graz
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Khalil Michael
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Voortman Margarete Maria
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- Abstract:
- BACKGROUND: Natalizumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS), which can diffuse in different anatomical compartments, including cerebrospinal fluid (CSF) and milk. OBJECTIVES: Starting from incidental detection of natalizumab in the CSF of MS patients, the objective of this study was to develope a flow-cytometry-based assay and apply it to quantify natalizumab in body fluids, including milk collected from nursing patients over 180 days and in patients with neutralizing antibodies against natalizumab. METHODS: CSF, milk and sera samples from patients with multiple sclerosis were tested by flow-cytometry for binding to a VLA-4 expressing cell line or to a control cell line. A standard curve was prepared by incubating the same cells with natalizumab at 50 μg/ml and serially diluted to 0.005 ng/ml. Binding specificity was confirmed using an anti-natalizumab neutralizing antibody. RESULTS: Our assay was sensitive enough to detect natalizumab in CSF, with a lower detection limit of 1.5 ng/ml. Neutralizing antibodies against natalizumab inhibited binding to the cell line. In breastmilk, the peak concentration was observed during the first 2 weeks after infusion and the average concentration over the observation time was 173.3 ng/ml, with a trend toward increased average milk concentration over subsequent administrations. CONCLUSION: Routine use of such an assay would enable a better understanding of the safety of therapeutic antibody administration during pregnancy and lactation.
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breastfeeding
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cerebrospinal fluid
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milk
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multiple sclerosis
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Natalizumab