title: Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study.
abstract: Neutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are the cause of acquired hemophilia A (AHA). They are quantified in the Bethesda assay or Nijmegen-modified Bethesda assay by their ability to neutralize FVIII in normal human plasma. However, FVIII inhibitors do not represent the whole spectrum of anti-FVIII autoantibodies. Here, we studied isotypes, immunoglobulin G subclasses, and apparent affinities of anti-FVIII autoantibodies to assess their prognostic value for the outcome in AHA. We analyzed baseline samples from patients enrolled in the prospective GTH-AH 01/2010 study. Our data suggest that anti-FVIII immunoglobulin A (IgA) autoantibodies are predictors of poor outcome in AHA. Anti-FVIII IgA-positive patients achieved partial remission similar to anti-FVIII IgA-negative patients but had a higher risk of subsequent recurrence. Consequently, IgA-positive patients achieved complete remission less frequently (adjusted hazard ratio [aHR], 0.35; 95% confidence interval [CI], 0.18-0.68; P < .01) and had a higher risk of death (aHR, 2.62; 95% CI, 1.11-6.22; P < .05). Anti-FVIII IgA was the strongest negative predictor of recurrence-free survival after achieving partial remission and remained significant after adjustment for baseline demographic and clinical characteristics. In conclusion, anti-FVIII IgA represents a potential novel biomarker that could be useful to predict prognosis and tailor immunosuppressive treatment of AHA.
authors.affiliation: Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
authors.forename: Andreas
authors.identifier: 0000-0002-3600-8536
authors.initials: A
authors.lastname: Tiede
authors.affiliation: Research and Innovation, Baxalta, Vienna, Austria;
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Hofbauer
authors.affiliation: Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
authors.forename: Sonja
authors.initials: S
authors.lastname: Werwitzke
authors.affiliation: Hematology and Hemostasis, Vienna Medical University, Vienna, Austria;
authors.forename: Paul
authors.initials: P
authors.lastname: Knöbl
authors.affiliation: Internal Medicine, Vivantes Clinic Friedrichshain, Berlin, Germany;
authors.forename: Saskia
authors.initials: S
authors.lastname: Gottstein
authors.affiliation: Hemostasis, Hemotherapy, and Transfusion Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany;
authors.forename: Rüdiger E
authors.initials: RE
authors.lastname: Scharf
authors.affiliation: Hematology and Oncology, Freiburg University Hospital, Freiburg, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Heinz
authors.affiliation: Clinical Hemostaseology and Transfusion Medicine, Saarland University Hospital, Homburg/Saar, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Groß
authors.affiliation: Hematology and Oncology, University Hospital Eppendorf, Hamburg, Germany; and.
authors.forename: Katharina
authors.initials: K
authors.lastname: Holstein
authors.affiliation: Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
authors.forename: Christiane
authors.initials: C
authors.lastname: Dobbelstein
authors.affiliation: Research and Innovation, Baxalta, Vienna, Austria;
authors.forename: Fritz
authors.initials: F
authors.lastname: Scheiflinger
authors.affiliation: Biometry, Hannover Medical School, Hannover, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Koch
authors.affiliation: Research and Innovation, Baxalta, Vienna, Austria;
authors.forename: Birgit M
authors.initials: BM
authors.lastname: Reipert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D018572:Disease-Free Survival; D005169:Factor VIII / Q000037:antagonists & inhibitors*; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000401:mortality / Q000628:therapy; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; C078147:F8 protein, human; D005169:Factor VIII