Abstract Number: OC 09.1
Meeting: ISTH 2020 Congress
Background: Development of alloantibodies against factor VIII (FVIII) is a major complication of replacement therapy in sever hemophilia A patients. However, absence of endogenous FVIII does not necessarily lead to the incidence of inhibitors. The maternal cells migrate into fetus tissue during pregnancy and stays beyond birth. Unlike cells harboring F8 mutations in host hemophilia A fetus, maternal chimeric cells are able to express FVIII albeit at low level, we thus speculate whether the maternal chimeric cells could induce tolerance toward FVIII and prevent development of inhibitors.
Aims: To investigate the association of maternal chimerism and development of factor VIII inhibitors in hemophilia A patients.
Methods: The study recruited 83 hemophilia A patient-mother pairs, including 25 patients with inhibitors. All patients presented sever deficiencies of FVIII caused by intron 22 inversions, large deletions, nonsense or frame shift mutations, and had been exposed to both plasma-derived and recombinant FVIII in replacement therapy. Three SNPs on X chromosome with high minor allele frequency (MAF) in Chinese were selected as marker for individual DNA identification. The degree of maternal chimerism was examined by droplet digital PCR. Multivariable logistic regression was conducted to test associations between presence of maternal chimerism and the development of inhibitors.
Results: Among 20 patients with SNP allele representing of maternal origin presented, only 2 (10%) had inhibitors developed, while in 63 patients who failed to have maternal SNP alleles detected, 23 (34.3%) were inhibitor positive (odds ratio: 5.18, 95%CI:1.10- 24.34) (P=0.037).
Conclusions: Maternal chimeric cell may have induced immune tolerance in hemophilia A patients and absence of maternal chimeric cell constitutes a risk factor for inhibitor development.
To cite this abstract in AMA style:Lu Y, Chen Z, Dai J, Wu X, Gu H, Li Z, Li J, Ding Q, Wu W, Wu R, Wang X. Maternal Microchimerism Protects Hemophilia A Patient from Inhibitor Development [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/maternal-microchimerism-protects-hemophilia-a-patient-from-inhibitor-development/. Accessed December 11, 2023.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/maternal-microchimerism-protects-hemophilia-a-patient-from-inhibitor-development/