title: Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay.
abstract: BACKGROUND
  The development of neutralizing antibodies, referred to as inhibitors, against factor VIII is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development.
  
  
  OBJECTIVE
  To assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes.
  
  
  METHODS
  A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients.
  
  
  RESULTS
  Assessments of antibody profiles showed that the presence of anti-FVIII IgG1 , IgG2 or IgG4 correlated qualitatively and quantitatively with the presence of an FVIII inhibitor as determined with the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to being NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and had anti-FVIII IgG1 later developed an inhibitor, as compared with two of 33 patients with a negative inhibitor history without anti-FVIII IgG1 .
  
  
  CONCLUSIONS
  These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing.
authors.affiliation: Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Boylan
authors.forename: A S
authors.initials: AS
authors.lastname: Rice
authors.forename: A L
authors.initials: AL
authors.lastname: Dunn
authors.forename: M D
authors.initials: MD
authors.lastname: Tarantino
authors.forename: D B
authors.initials: DB
authors.lastname: Brettler
authors.forename: J C
authors.initials: JC
authors.lastname: Barrett
authors.forename: C H
authors.initials: CH
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005169:Factor VIII / Q000276:immunology*; D016231:Fluorescence Polarization Immunoassay / Q000379:methods*; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; C078147:F8 protein, human; D005169:Factor VIII
keywords: factor VIII; factor VIII deficiency; hemophilia A; immunoassay; inherited blood coagulation disorders