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  • Anti–factor VIII IgA as a p...
    Tiede, Andreas; Hofbauer, Christoph J.; Werwitzke, Sonja; Knöbl, Paul; Gottstein, Saskia; Scharf, Rüdiger E.; Heinz, Jürgen; Groß, Jürgen; Holstein, Katharina; Dobbelstein, Christiane; Scheiflinger, Fritz; Koch, Armin; Reipert, Birgit M.

    Blood, 05/2016, Letnik: 127, Številka: 19
    Journal Article

    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. •This study is the first to assess the prognostic value of FVIII-specific antibody data in patients with AHA.•Anti-FVIII IgA, but not immunoglobulin G, autoantibodies at baseline are potential predictors of recurrence and poor outcome of AHA.