Effect of the First Factor VIII Infusions on Immunological Biomarkers in Previously Untreated Patients with Hemophilia A from the HEMFIL Study.

Autor:	de Oliveira LMM; Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Jardim LL; Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.; Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands., Santana MAP; Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil., Cerqueira MH; Instituto de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO), Rio de Janeiro, Brazil., Lorenzato CS; Centro de Hematologia e Hemoterapia do Paraná (HEMEPAR), Curitiba, Brazil., Franco VKB; Centro de Hematologia e Hemoterapia de Santa Catarina (HEMOSC), Florianópolis, Brazil., Zuccherato LW; Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.; Instituto Mário Penna, Belo Horizonte, Minas Gerais, Brazil., Rezende SM; Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Chaves DG; Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil.
Jazyk:	angličtina
Zdroj:	Thrombosis and haemostasis [Thromb Haemost] 2021 Jul; Vol. 121 (7), pp. 891-899. Date of Electronic Publication: 2021 Jan 10.
DOI:	10.1055/s-0040-1722353
Abstrakt:	Hemophilia A (HA) is an inherited bleeding disorder which requires continuous replacement with factor (F) VIII concentrate. The main complication of HA is the development of neutralizing alloantibodies which inhibit FVIII activity (inhibitors). The objective of this study was to investigate the effect of the first FVIII infusions on immunological biomarkers in previously untreated patients with HA. Plasma samples were collected at enrollment before any FVIII infusion (T0) and at inhibitor development (INB +/T1) or up to 35 exposure days without inhibitors (INB -/T1). Anti-FVIII antibodies (immunoglobulin M, immunoglobulin G [IgG] 1, IgG3, and IgG4), chemokines (CCL2, CCL5, CXCL8, CXCL9, and CXCL10), and cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, interferon-γ, tumor necrosis factor, and IL-17) were assessed. A total of 71 children with severe HA were included, of whom 28 (39.4%) developed inhibitors. Plasma levels of anti-FVIII IgG4, IL-6, and CXCL8 were higher at INB +/T1 when compared with INB -/T1. This group presented a mixed cytokine profile and higher plasma levels of CXCL9 and CXL10 when compared with INB +/T1. We conclude that exposure to FVIII triggers a proinflammatory response mediated by IL-6 and CXCL8 in patients with HA who developed inhibitors. Regardless of inhibitor status, the immune system of all HA patients is stimulated after infusions of FVIII. Competing Interests: M.H.C. reports grants and personal fees from Novo Nordisk, Takeda, Biomarin, Pfizer, CSL Behring, and Roche. The other authors do not report conflicts of interest. (Thieme. All rights reserved.)
Databáze:	MEDLINE
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