High levels of anti–factor VIII immunoglobulin G4 and immunoglobulin G total are associated with immune tolerance induction failure in people with congenital hemophilia A and high-responding inhibitors

• Published in: Research and practice in thrombosis and haemostasis 2024-05, Vol.8 (4), p.102436-102436, Article 102436
• Main Authors: Chaves, Daniel Gonçalves, da Silva Santos, Brendon Ayala, Zucherato, Luciana Werneck, Dias, Maíse Moreira, Lorenzato, Claudia Santos, de Oliveira, Andrea Gonçalves, Cerqueira, Mônica Hermida, de Albuquerque Ribeiro, Rosângela, Etto, Leina Yukari, Franco, Vivian Karla Brognoli, Roberti, Maria do Rosário Ferraz, de Araújo Callado, Fábia Michelle Rodrigues, de Cerqueira, Maria Aline Ferreira, Pinto, Ieda, Camelo, Ricardo Mesquita, Rezende, Suely Meireles
• Format: Article
• Language: English
• Subjects: alloantibodies; Brief Report; chemokine; cytokine; factor VIII; hemophilia A; immune tolerance
• ISSN: 2475-0379; 2475-0379
• DOI: 10.1016/j.rpth.2024.102436

Immune tolerance induction (ITI) is the treatment of choice to eradicate neutralizing anti–factor (F)VIII alloantibodies (inhibitors) in people with inherited hemophilia A. However, it is not successful in 10% to 40% of the cases. The biological mechanisms and biomarkers associated with ITI outcome are largely unknown. The aim of this study was to investigate the association of plasma cytokines (interferon-γ, tumor necrosis factor, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-10, and IL-17A), chemokines (IL-8/CXCL8, RANTES/CCL5, MIG/CXCL9, MCP-1/CCL2, and IP-10/CXCL10), and anti-FVIII immunoglobulin (Ig) G total, IgG1, and IgG4 with ITI outcome. In this cross-sectional analysis of the Brazilian Immune Tolerance Study, we assessed plasma levels of anti-FVIII IgGs using an enzyme-linked immunosorbent assay with plasma-derived FVIII and recombinant FVIII as target antigens, immobilized in microplates. We assayed 98 plasma samples of moderately severe and severe (FVIII activity,