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Anti-factor VIII antibodies in brothers with haemophilia A share similar characteristics.
Kahle, J; Orlowski, A; Stichel, D; Healey, J F; Parker, E T; Donfield, S M; Astermark, J; Berntorp, E; Lollar, P; Schwabe, D; Königs, C.
Afiliação
  • Kahle J; Department of Paediatrics, Clinical and Molecular Haemostasis and Immunodeficiency, University Hospital Frankfurt, Frankfurt am Main, Germany.
  • Orlowski A; Department of Paediatrics, Clinical and Molecular Haemostasis and Immunodeficiency, University Hospital Frankfurt, Frankfurt am Main, Germany.
  • Stichel D; Department of Paediatrics, Clinical and Molecular Haemostasis and Immunodeficiency, University Hospital Frankfurt, Frankfurt am Main, Germany.
  • Healey JF; Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, GA, USA.
  • Parker ET; Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, GA, USA.
  • Donfield SM; Department of Biostatistics, Rho Inc., Chapel Hill, NC, USA.
  • Astermark J; Centre for Thrombosis and Haemostasis, Lund University, Skåne University Hospital, Malmö, Sweden.
  • Berntorp E; Centre for Thrombosis and Haemostasis, Lund University, Skåne University Hospital, Malmö, Sweden.
  • Lollar P; Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, GA, USA.
  • Schwabe D; Department of Paediatrics, Clinical and Molecular Haemostasis and Immunodeficiency, University Hospital Frankfurt, Frankfurt am Main, Germany.
  • Königs C; Department of Paediatrics, Clinical and Molecular Haemostasis and Immunodeficiency, University Hospital Frankfurt, Frankfurt am Main, Germany.
Haemophilia ; 23(2): 292-299, 2017 Mar.
Article em En | MEDLINE | ID: mdl-27862687
INTRODUCTION: 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. AIM: To analyze the influence of genetic factors on the nature of the humoral immune response to FVIII in eight brother pairs with inhibitors. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator VIII / Hemofilia A / Anticorpos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Haemophilia Assunto da revista: HEMATOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator VIII / Hemofilia A / Anticorpos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Haemophilia Assunto da revista: HEMATOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido