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Long-term anti-FVIII antibody response in Bethesda-negative haemophilia A patients receiving continuous replacement therapy.

Klintman, Jenny LU ; Hillarp, Andreas LU ; Berntorp, Erik LU and Astermark, Jan LU (2013) In British Journal of Haematology 163(3). p.385-392
Abstract
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 4 years with the goal of exploring the long-term development of NNA using an enzyme-linked immunosorbent assay (ELISA). Ten of 78 subjects (12·8%)... (More)
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 4 years with the goal of exploring the long-term development of NNA using an enzyme-linked immunosorbent assay (ELISA). Ten of 78 subjects (12·8%) 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-à-cath implantation and HCV infection were shown. Interestingly, patients with NNA had significantly fewer bleeding episodes (P = 0·048) 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Haematology
volume
163
issue
3
pages
385 - 392
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000325548800014
  • pmid:24032553
  • scopus:84885423738
ISSN
0007-1048
DOI
10.1111/bjh.12540
language
English
LU publication?
yes
id
8be17c9b-de0b-41ae-a2d3-37959004c6f8 (old id 4065900)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24032553?dopt=Abstract
date added to LUP
2013-10-02 18:49:08
date last changed
2019-10-08 01:19:52
@article{8be17c9b-de0b-41ae-a2d3-37959004c6f8,
  abstract     = {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 4 years with the goal of exploring the long-term development of NNA using an enzyme-linked immunosorbent assay (ELISA). Ten of 78 subjects (12·8%) 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-à-cath implantation and HCV infection were shown. Interestingly, patients with NNA had significantly fewer bleeding episodes (P = 0·048) 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.},
  author       = {Klintman, Jenny and Hillarp, Andreas and Berntorp, Erik and Astermark, Jan},
  issn         = {0007-1048},
  language     = {eng},
  number       = {3},
  pages        = {385--392},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {Long-term anti-FVIII antibody response in Bethesda-negative haemophilia A patients receiving continuous replacement therapy.},
  url          = {http://dx.doi.org/10.1111/bjh.12540},
  volume       = {163},
  year         = {2013},
}