The following review focuses on the current view of risk factors for the development of inhibitory antibodies and whether this risk can be modulated and minimized. Treatment of haemophilia using replacement of the deficient factor has substantially improved over recent decades and life expectancy for a young boy suffering from severe haemophilia A is today, in most developed countries, similar to that of his healthy peers [1, 2]. However, severe adverse effects of replacement therapy, such as the development of neutralizing inhibitory antibodies, remain

a threat and should be considered in the management of patients. Most inhibitory antibodies will be eliminated by the use of immune tolerance Ponatinib cost induction (ITI) with or without immunosuppression, but ITI is costly and the outcome this website unpredictable [3]. Therefore, it is important to fully elucidate the factors that influence inhibitor development in one-third of patients with severe haemophilia A. This overview will summarize the current view of these risk factors in light of the immune response taking place, and will address the issue of whether it will be possible to minimize risk in the future. The mechanisms by

which inhibitory antibodies develop have been carefully studied for several years and major advances in our understanding have been made [4, 5]. However, much still remains to be resolved, and it is clear that there are several

processes that potentially influence the outcome. These include the methods by which antigen-presenting cells (APC) process and present the endocytosed factor VIII molecule to the T-helper cells, the nature of the T and B cells and the profile of the immune-regulatory molecules, including both cell-bound molecules and those secreted into the circulation (Fig. 1). In addition, regulatory T cells with suppressor activities are of major importance MCE公司 and a number of initiatives are now underway to fully appreciate the impact of these cells and to define how this knowledge may be used to modify the immune response [6]. Different subsets of these T cells have been described, such as CD4+ CD25+ FoxP3+ Treg cells, IL-10-producing Tr1 cells, transforming growth factor-β-producing Th3 cells and CD8+ Treg cells. Interestingly, an immune response not dependent on T-helper cells has recently been suggested, but so far the clinical significance of this type of immune response is not completely clear [7]. It appears that predominantly low-affinity antibodies are produced by this route and may therefore be of relevance for non-inhibitory or non-neutralizing antibodies. The reason why these antibodies can be identified in some patients but not others, and are also found in patients without haemophilia, is not known.