Correlations of Plasma Cytokine Levels and Anti-FVIII Antibodies during Immune Tolerance Induction

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.2471-2471
• Main Authors: Hartmann, Johannes, Schmidt, Anja, Beilfuss, Marko, Stichel, Diana, Heller, Christine, Schwabe, Dirk, Klingebiel, Thomas, Ewing, Nadia P, Koenigs, Christoph
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-110588

Introduction The development of neutralizing anti-FVIII antibodies (inhibitors) with reduced or absent activity of substituted factor VIII (FVIII) remains the most serious complication of hemophilia A therapy (Kempton, 2014). Frequent and high doses of FVIII with or without bypassing products can reestablish immune tolerance in 60-70% of patients. Polymorphism in immune response genes including IL-10 and TNFa were identified as risk factors for inhibitor development (Astermark, 2006). Cross-sectional studies showed different cytokine profiles in patients with hemophilia, especially in those with history of an inhibitor (Oliveira, 2013). In this study cytokine profiles were monitored longitudinally during immune tolerance induction (ITI). Methods 107 plasma samples from 18 patients were collected during the RES.I.S.T Experienced and Naive trial, which included patients with a poor prognosis for ITI success (Gringeri, 2007). We quantified 14 cytokines in each sample by using a Human High Sensitivity T-Cell Discovery Array 14-Plex (Eve Technologies Corp, Calgary, AB, Canada). ELISA based FVIII antibody assays were used for anti-FVIII IgG detection. FVIII inhibitor titers (Bethesda assay, BU) were measured and available for the analysis. The cut-off for a positive inhibitor was >0,6 BU mL-1. Bethesda titers (BUpos) between 0,6 -