Immune-monitoring of haemophilia A patients undergoing ITI
Despite clinical experience with the different protocols of ITI, little is known about the immunological mechanisms that cause the downregulation of FVIII-specific immune responses and the induction of long-lasting immune tolerance against FVIII. S. Lacroix-Desmazes will monitor and analyze the modifications of the immune system and the inflammatory status of the patient during the course of ITI.
Some clinically relevant immune markers (IMs) might help to predict the positive or negative outcome of the ITI.
The FVIII-inhibitor plasma may be able to affect the differentiation and maturation state of dendritic cells from healthy blood donors.
Both, cells and plasma collected during the course of ITI therapy will be required to study the IMs in haemophilia A patients with inhibitors. Depending on the amount of blood collected, the IMs will be studied with the following priority:
- IM1: Different subpopulations of circulating T cells
- IM2: Number, maturation state and endocytotic capacity of different antigen-presenting cells
- IM3: Circulating cells that have endocytosed FVIII
- IM4: Number of FVIII-specific B cells
- IM5: Will be studied in any case
Also, quantitative measurements of different interleukins involved in the immune response including INF-γ, TGF-β1 and TNF-α in plasma will be done.
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- Lacroix-Desmazes S et al. Dynamics of factor VIII interactions determine its immunologic fate in haemophilia A. Blood 2008; 12(2): 240-49.
- Wroblewska A et al. Dangerous liaisons: how the immune system deals with factor VIII. J Thromb Haemost 2013; 11(1): 47-55.
- Navarrete AM et al. Endocytic receptor for pro-coagulant factor VIII: relevance to inhibitor formation. Thromb Haemost 2010; 104(6): 1093-98.
- Chaves DG et al. A shift towards a T cell cytokine deficiency along with an antiinflammatory/regulatory microenvironment may enable the synthesis of anti-FVIII inhibitors in haemophilia A patients. Clin Exp Immunol 2010; 162(3): 425-37.