Isotypic analysis of antibodies against activated Factor VII in patients with Factor VII deficiency using the x-MAP technology. Issue 141 (May 2016)

• Record Type: Journal Article
• Authors: Pfeiffer, Caroline; Mathieu-Dupas, Eve; Logghe, Pauline; Lissalde-Lavigne, Géraldine; Balicchi, Julien; Caliskan, Umran; Valentin, Thomas; Laune, Daniel; Molina, Franck; Schved, Jean François; Giansily-Blaizot, Muriel
• Is Part Of: Thrombosis research. Issue 141(2016)
• Page Start: 22
• Page End: 27
• Publication Date: 2016-05
• Subjects: Factor VII -- Factor VII deficiency -- anti-FVII antibodies -- x-MAP technology -- Bethesda assay; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2016.02.021
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: While the immune response to hemophilic factors in hemophilia has been widely studied, little is known about the development of anti-Factor VII (FVII) antibodies in FVII deficiency. We developed a robust technique based on the x-MAP technology to detect the presence of antibodies against FVII and characterize their isotype and validated this method using blood samples from 100 patients with FVII deficiency (median FVII clotting activity [FVII:C]: 6%) and 95 healthy controls. Anti-FVII antibodies were detected in patients but also in some controls, although the concentration of total immunoglobulin G (IgGt) and IgG1 and IgG4 subclasses was significantly different between groups. The IgG1 subclass concentrations remained significantly different also when only untreated patients were compared with controls. This difference could partially be related to the F7 genotype, particularly in patients harboring the p.Arg139Gln mutation. This x-MAP-based method might be useful for assessing the immunogenicity of novel FVII compounds and of activated FVII (FVIIa) concentrates. Further prospective studies are needed to better understand the clinical relevance of these antibodies in the management of patients with FVII deficiency. Highlights: There is a natural specific immune response against activated Factor VII. Deleterious F7 alleles may be associated with FVII inhibitor occurrence. The p.Arg139Gln variant may be associated with anti-FVII non-neutralizing antibody occurrence. The x-MAP technology is a valuable tool for assessing the FVII immune response.