Abstract Number: PB0834
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Basic
Background: Hemophilia A (HA) is an X-linked bleeding disorder caused by factor VIII (FVIII) deficiency. Upon replacement of the missing clotting factor by intravenous infusions, around 30% of patients develop neutralizing antibodies (inhibitors). Their formation involves the activation of both the innate and adaptive arm of the immune system and might be related to the absence of immunological tolerance to FVIII.
Aims: Little is known about the development and function of the immune system in HA patients prior to treatment. Discovering any intrinsic alteration would help to understand the pathogenesis of inhibitor formation and to develop new therapies. As such, we sought to analyze the numbers and phenotype of different immune cells in a mouse model of severe HA.
Methods: Single cell suspensions were obtained from several organs collected at different timepoints from HA and age-matched wild-type (wt) mice. Cell numbers were determined by Trypan blue count while percentages and phenotype of immune cells evaluated by flow cytometry.
Results: At week 8 both splenic CD4 and CD8 T cells were significantly lower in HA compare to wt mice. This difference disappeared at later timepoints (52 weeks). Interestingly even CD4 T regulatory cells were decreased in the spleen of HA mice. Thymic count and cell composition were similar between the two groups, suggesting that the difference observed in periphery was not due to a reduced thymic output or an impaired T cell development.
Conclusions: Our preliminary data support the hypothesis that the absence of FVIII could affect the immune cell populations. The decreased T cell count found in the spleen of HA mice is intriguing since they are highly involved in the inhibitor formation. Studies are currently ongoing for understanding the basis and significance of this reduction.
To cite this abstract in AMA style:
Borsotti C, Kalandadze V, Mohammed I, Di Simone P, Follenzi A. Reduced Splenic T Cells Count in an Untreated Mouse Model of Severe Hemophilia A [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/reduced-splenic-t-cells-count-in-an-untreated-mouse-model-of-severe-hemophilia-a/. Accessed March 21, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/reduced-splenic-t-cells-count-in-an-untreated-mouse-model-of-severe-hemophilia-a/