Why do inhibitors develop? Principles of and factors influencing the risk for inhibitor development in haemophilia

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia Vol. 12; no. s3; pp. 52 - 60
• Main Author: ASTERMARK, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2006
• Subjects: Blood Coagulation Factor Inhibitors - biosynthesis; Clinical Medicine; Factor IX - antagonists & inhibitors; Factor IX - immunology; Factor VIII - antagonists & inhibitors; Factor VIII - immunology; Genotype; haemophilia; Hematologi; Hematology; Hemophilia A - genetics; Hemophilia A - immunology; Hemophilia B - genetics; Hemophilia B - immunology; Humans; inhibitors; Isoantibodies - biosynthesis; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Risk Factors
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/j.1365-2516.2006.01261.x

The formation of inhibitory alloantibodies is, in the postinfectious era, the most severe and costly complication of replacement therapy in patients with haemophilia. The complexity of the immune response to the infused factor becomes more and more obvious as knowledge in the area increases. Antibodies develop as a result of a complex multi‐factorial interaction between antigen‐presenting cells, T‐ and B‐lymphocytes. Genetic susceptibility of cell surface molecules, such as the major histocompatibility complex, the T‐cell receptor and cytokine receptors, as well as various immunomodulatory molecules have a major impact on the outcome. In addition, environmental factors probably influence the risk of inhibitor development. The current concept of inhibitor development is reviewed. A better understanding of the pathophysiological mechanisms involved will facilitate improvement of therapy in the future, and hopefully provide an opportunity to prevent this complication of treatment.