| Autor: |
Karim, Ahmad Faisal, Vir, Pooja, Gunasekera, Devi, Stering, Allen I., Lieuw, Kenneth, Pratt, Kathleen P. |
| Zdroj: |
Blood; November 2019, Vol. 134 Issue: 1, Number 1 Supplement 1 p2413-2413, 1p |
| Abstrakt: |
The existence of natural antibodies recognizing endogenous factor VIII (FVIII) and of FVIII-specific CD4+T-cell responses in some healthy, non-hemophilic blood donors has been appreciated for >20 years. The Conti-Fine group measured CD4+T-cell proliferation following in vitrostimulation with FVIII protein or synthetic FVIII peptides. More recently, FVIII-specific CD4+T-cell lines were expanded from PBMCs isolated from large blood volumes donated by healthy individuals, and estimates of specific precursor frequency (~2/million CD4+T cells) were calculated on the basis of interferon (IFN)-gamma ELISPOT assays of FVIII-stimulated cells (Meuniere et al., Blood Advances 1(21): 1842-7). Escape of these self-reactive precursor cells from thymic editing via deletion or anergy and their subsequent persistence in the periphery may contribute to the rare but potentially severe autoimmune reactions to FVIII (“acquired hemophilia A”) and to the unusual immunogenicity of therapeutic FVIII administered i.v. to hemophilia A patients. |
| Databáze: |
Supplemental Index |
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