Send to

Choose Destination
Haemophilia. 2017 Mar;23(2):292-299. doi: 10.1111/hae.13105. Epub 2016 Nov 8.

Anti-factor VIII antibodies in brothers with haemophilia A share similar characteristics.

Author information

Department of Paediatrics, Clinical and Molecular Haemostasis and Immunodeficiency, University Hospital Frankfurt, Frankfurt am Main, Germany.
Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, GA, USA.
Department of Biostatistics, Rho Inc., Chapel Hill, NC, USA.
Centre for Thrombosis and Haemostasis, Lund University, Skåne University Hospital, Malmö, Sweden.



The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) is currently the most serious complication for patients with haemophilia A undergoing FVIII replacement therapy. Several genetic factors have been acknowledged as risk factors for inhibitor development.


To analyze the influence of genetic factors on the nature of the humoral immune response to FVIII in eight brother pairs with inhibitors.


The domain specificity of FVIII-specific IgG was analysed by antibody binding to FVIII fragments and homologue-scanning mutagenesis (HSM). The FVIII-specific IgG subclasses were measured by direct ELISA.


Of the 16 patient analysed with both methods, 12 had A2- and 13 had C2-specific IgG. The presence of A1-, A3- or C1-specific IgG was identified in nine of 14 patients analysed by HSM. IgG1, IgG2 and IgG4 subclasses contributed to the anti-FVIII IgG response, and the amount of FVIII-specific IgG1 (r = 0.66) and IgG4 (r = 0.69) correlated significantly with inhibitor titres. Patients with high concentrations of total anti-FVIII IgG (r = 0.69) or high inhibitor titres (r = 0.52) had a high proportion of FVIII-specific IgG4. Statistical analysis revealed trends/evidence that the subclass distribution (P = 0.0847) and domain specificity to HC/LC (P = 0.0883) and A2/C2 (P = 0.0011) of anti-FVIII IgG were more similar in brothers compared to unrelated subjects.


Overall, our data provide a first hint that anti-FVIII IgG characteristics are comparable among haemophilic brothers with inhibitors. Whether genetic factors also influence the nature of patients' antibodies needs to be confirmed in a larger study population.


IgG subclasses; anti-factor VIII antibodies; epitope mapping; factor VIII inhibitors; haemophilia A

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center