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Thromb Res. 2016 May;141:22-7. doi: 10.1016/j.thromres.2016.02.021. Epub 2016 Feb 23.

Isotypic analysis of antibodies against activated Factor VII in patients with Factor VII deficiency using the x-MAP technology.

Author information

1
SysDiag UMR3145 CNRS/Bio-Rad, Montpellier, France; Department of Biological Hematology, Hospital Saint-Eloi, Montpellier, France.
2
SysDiag UMR3145 CNRS/Bio-Rad, Montpellier, France.
3
NEU Meram Medical Faculty Hospital, Department of Pediatric Hematology, Konya, Turkey.
4
Department of Biological Hematology, Hospital Saint-Eloi, Montpellier, France.
5
Department of Biological Hematology, Hospital Saint-Eloi, Montpellier, France. Electronic address: m-giansily@chu-montpellier.fr.

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.

KEYWORDS:

Bethesda assay; Factor VII; Factor VII deficiency; anti-FVII antibodies; x-MAP technology

PMID:
26962982
DOI:
10.1016/j.thromres.2016.02.021
[Indexed for MEDLINE]

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