期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 163, 期 3, 页码 385-392出版社
WILEY-BLACKWELL
DOI: 10.1111/bjh.12540
关键词
haemophilia A; factor VIII; immunogenicity; clotting factors; non-neutralizing anti-FVIII antibodies
类别
资金
- Bayer Healthcare
It has previously been shown that patients with haemophilia A may develop non-neutralizing anti-factor VIII (FVIII) antibodies (NNA) that escape detection by the Bethesda assay, but are detected using immune-based assays. We and others found NNAs to be directed not only towards non-functional parts of the protein, but towards all regions of the FVIII protein. We also showed a heterogeneous antibody response towards different FVIII products. However, the clinical relevance and the natural history of NNA remain unclear. Therefore, we followed a cohort of unrelated subjects with haemophilia A for 4years with the goal of exploring the long-term development of NNA using an enzyme-linked immunosorbent assay (ELISA). Ten of 78 subjects (12 center dot 8%) exhibited an immune response that was transient and heterogeneous, and none of the subjects developed an FVIII inhibitor. The result of the ELISA was examined in relation to clinical variables and no significant associations between a positive ELISA and age, F8 mutation, port-a-cath implantation and HCV infection were shown. Interestingly, patients with NNA had significantly fewer bleeding episodes (P=0 center dot 048) compared with NNA-negative subjects. The results indicate that the immune response to FVIII products within an individual may vary over time. However, the clinical impact of NNA remains unclear.
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