title: Isotypic analysis of antibodies against activated Factor VII in patients with Factor VII deficiency using the x-MAP technology.
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.
authors.affiliation: SysDiag UMR3145 CNRS/Bio-Rad, Montpellier, France; Department of Biological Hematology, Hospital Saint-Eloi, Montpellier, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Pfeiffer
authors.affiliation: SysDiag UMR3145 CNRS/Bio-Rad, Montpellier, France.
authors.forename: Eve
authors.initials: E
authors.lastname: Mathieu-Dupas
authors.affiliation: SysDiag UMR3145 CNRS/Bio-Rad, Montpellier, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Logghe
authors.affiliation: SysDiag UMR3145 CNRS/Bio-Rad, Montpellier, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Lissalde-Lavigne
authors.affiliation: SysDiag UMR3145 CNRS/Bio-Rad, Montpellier, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Balicchi
authors.affiliation: NEU Meram Medical Faculty Hospital, Department of Pediatric Hematology, Konya, Turkey.
authors.forename: Umran
authors.initials: U
authors.lastname: Caliskan
authors.affiliation: Department of Biological Hematology, Hospital Saint-Eloi, Montpellier, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Valentin
authors.affiliation: SysDiag UMR3145 CNRS/Bio-Rad, Montpellier, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Laune
authors.affiliation: SysDiag UMR3145 CNRS/Bio-Rad, Montpellier, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Molina
authors.affiliation: Department of Biological Hematology, Hospital Saint-Eloi, Montpellier, France.
authors.forename: Jean François
authors.initials: JF
authors.lastname: Schved
authors.affiliation: Department of Biological Hematology, Hospital Saint-Eloi, Montpellier, France. Electronic address: m-giansily@chu-montpellier.fr.
authors.forename: Muriel
authors.initials: M
authors.lastname: Giansily-Blaizot
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005167:Factor VII / Q000276:immunology*; D005168:Factor VII Deficiency / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D015942:Factor VIIa / Q000276:immunology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007223:Infant; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: Bethesda assay; Factor VII; Factor VII deficiency; anti-FVII antibodies; x-MAP technology