Cytokine profile and FVIII inhibitors development in haemophilia A

Summary Haemophilia A is a hereditary bleeding disorder linked to the X chromosome characterized by a deficiency or defect in the coagulation factor VIII (FVIII). Individuals with this coagulopathy require constant infusions of FVIII to maintain their physical integrity and haemostasis. During treat...

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Bibliographic Details
Published in:	Haemophilia : the official journal of the World Federation of Hemophilia Vol. 19; no. 3; pp. e139 - e142
Main Authors:	Oliveira, C. A., Velloso-Rodrigues, C., Machado, F. C. J., Carvalho, B. N., Gentz, S. H. L., Martins-Filho, O. A., Chaves, D. G.
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01-05-2013
Subjects:	Adolescent Adult Antibodies Blood Coagulation Factor Inhibitors - blood Child Child, Preschool cytokine profile Cytokines - blood Factor VIII - antagonists & inhibitors Factor VIII - metabolism Factor VIII - therapeutic use FVIII inhibitors haemophilia A Hemophilia A - drug therapy Hemophilia A - metabolism Hemophilia A - pathology Humans Interferon-gamma - blood Interleukin-10 - blood Interleukin-2 - blood Interleukin-4 - blood Interleukin-5 - blood Male Middle Aged Tumor Necrosis Factor-alpha - blood Young Adult
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Summary:	Summary Haemophilia A is a hereditary bleeding disorder linked to the X chromosome characterized by a deficiency or defect in the coagulation factor VIII (FVIII). Individuals with this coagulopathy require constant infusions of FVIII to maintain their physical integrity and haemostasis. During treatment, some patients develop an immune response that produces antibodies to FVIII, also called inhibitors, affecting the pro‐coagulant activity of this protein. Despite the clinical relevance of FVIII inhibitors, the immune mechanisms that lead to their production are not known. This study investigated the immunological cytokine profile using plasma from HA patients which were either positive or negative for FVIII inhibitors and from healthy individuals. The results showed that healthy individuals and HA patients that do not develop FVIII inhibitors have a mixed immune response profile with high secretion of IFN‐γ, TNF‐α IL‐2 and IL‐5. In contrast, HA patients with FVIII inhibitors exhibited an anti‐inflammatory/regulatory immune response characterized by low levels of all measured cytokines except for IL‐4 and IL‐10. This profile may be related to the development and maintenance of the FVIII inhibitors. By comparing the cytokine profiles of the three different groups we have established a model explaining the immune activation resulting in the production of FVIII inhibitors in haemophilia A patients.
Bibliography:	istex:0B68E3460D5EC2F7A483B7A8E281646DDE4FC4CA ark:/67375/WNG-KQ3MRJBV-Z Conselho Nacional de Desenvolvimento Científico e Tecnológico ArticleID:HAE12096 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1351-8216 1365-2516
DOI:	10.1111/hae.12096