Article Dans Une Revue Journal of Thrombosis and Haemostasis Année : 2024

The use of 1E12, a monoclonal anti-platelet factor 4 antibody, to improve the diagnosis of vaccine-induced immune thrombotic thrombocytopenia

1 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
2 ISCHEMIA - Membrane Signalling and Inflammation in reperfusion Injuries
3 McMaster University [Hamilton, Ontario]
4 CHU Charleroi - Centre Hospitalier Universitaire de Charleroi-Chimay
5 LilNCog - Lille Neurosciences & Cognition - U 1172
6 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
7 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
8 CHU Dijon
9 CHU Limoges
10 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
11 LVTS (UMR_S_1148 / U1148) - Laboratoire de Recherche Vasculaire Translationnelle
12 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
13 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
14 Irset - Institut de recherche en santé, environnement et travail
15 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
16 CHU Angers - Centre Hospitalier Universitaire d'Angers
17 CRCI2NA - Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers
18 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
19 UCL - Université Catholique de Louvain = Catholic University of Louvain
20 Hôpital Lariboisière-Fernand-Widal [APHP]
21 IThEM - U1140 - Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis
22 EGID - Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508
23 RNMCD - Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011
Emmanuel De Maistre
Magali Donnard
  • Fonction : Auteur

Résumé

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a complication of adenoviral-based vaccine against SARS-CoV-2 due to prothrombotic immunoglobulin (Ig) G antibodies to platelet factor 4 (PF4) and may be difficult to distinguish from heparin-induced thrombocytopenia (HIT) in patients treated with heparin. OBJECTIVES: We assessed the usefulness of competitive anti-PF4 enzyme immunoassays (EIAs) in this context. METHODS: The ability of F(ab’)2 fragments of 1E12, 1C12, and 2E1, 3 monoclonal anti-PF4 antibodies, to inhibit the binding of human VITT or HIT antibodies to PF4 was evaluated using EIAs. Alanine-scanning mutagenesis was performed to define the amino acids involved in the interactions between the monoclonal antibodies and PF4. RESULTS: A strong inhibition of VITT IgG binding to PF4 was measured with 1E12 (median inhibition, 93%; n = 8), whereas it had no effect on the binding of HIT antibodies (median, 6%; n = 8). In contrast, 1C12 and 2E1 inhibited VITT (median, 74% and 76%, respectively) and HIT antibodies (median, 68% and 53%, respectively) binding to PF4. When a competitive anti-PF4 EIA was performed with 1E12 for 19 additional VITT samples, it strongly inhibited IgG binding to PF4, except for 1 patient, who had actually developed HIT according to the clinical history. Epitope mapping showed that 1E12 interacts with 5 key amino acids on PF4, of which 4 are also required for the binding of human VITT antibodies, thus explaining the competitive inhibition. CONCLUSION: A simple competitive anti-PF4 EIA with 1E12 could help confirm VITT diagnosis and distinguish it from HIT in patients when both diagnoses are possible.
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hal-04615960 , version 1 (02-07-2024)

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Caroline Vayne, Jérôme Rollin, Rumi Clare, Mercy Daka, Merveille Atsouawe, et al.. The use of 1E12, a monoclonal anti-platelet factor 4 antibody, to improve the diagnosis of vaccine-induced immune thrombotic thrombocytopenia. Journal of Thrombosis and Haemostasis, 2024, 22 (8), pp.2306-2315. ⟨10.1016/j.jtha.2024.05.005⟩. ⟨hal-04615960⟩
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