Abstract
Most plasmas from patients with inhibitors contain antibodies that are reactive with the C2 domain of factor VIII. Previously, we have shown that the variable heavy chain (V(H)) regions of antibodies to the C2 domain are encoded by the closely related germline gene segments DP-10, DP-14, and DP-88, which all belong to the V(H)1 gene family. Here, we report on the isolation and characterization of additional anti-C2 antibodies that are derived from V(H) gene segments DP-88 and DP-5. Competition experiments using murine monoclonal antibodies CLB-CAg 117 and ESH4 demonstrated that antibodies derived from DP-5 and DP-88 bound to different sites within the C2 domain. Epitope mapping studies using a series of factor VIII/factor V hybrids revealed that residues 2223 to 2332 of factor VIII are required for binding of the DP-10-, DP-14-, and DP-88-encoded antibodies. In contrast, binding of the DP-5-encoded antibodies required residues in both the amino- and carboxy-terminus of the C2 domain. Inspection of the reactivity of the antibodies with a series of human/porcine hybrids yielded similar data. Binding of antibodies derived from germline gene segments DP-10, DP-14, and DP-88 was unaffected by replacement of residues 2181 to 2243 of ...Continue Reading
Citations
Jan 6, 2005·Springer Seminars in Immunopathology·Carl S Goodyear, Gregg J Silverman
Jan 24, 2009·Clinical Reviews in Allergy & Immunology·Sebastien AndréSuryasarathi Dasgupta
Feb 3, 2009·Clinical Reviews in Allergy & Immunology·Kathleen P Pratt, Arthur R Thompson
Jul 17, 2004·Current Opinion in Hematology·Marc G Jacquemin, Jean-Marie R Saint-Remy
May 13, 2008·Blood·Sébastien Lacroix-DesmazesSuryasarathi Dasgupta
Nov 1, 2005·BMC Genomics·Ramy A Arnaout
Mar 4, 2006·International Journal of Hematology·Midori Shima
Jan 10, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Leonard MoiseDavid W Scott
Oct 4, 2011·The Journal of Allergy and Clinical Immunology·Eszter HerczenikJan Voorberg
Jul 29, 2011·The Science of the Total Environment·Roberta CarafaPeter Carsten von der Ohe
Jan 22, 2005·Transfusion·Gregg J SilvermanDon L Siegel
Oct 14, 2004·Haemophilia : the Official Journal of the World Federation of Hemophilia·S W PipeC E Walsh
Jun 29, 2004·Journal of Thrombosis and Haemostasis : JTH·P Lollar
May 20, 2003·Scandinavian Journal of Immunology·Ø IhleT E Michaelsen
Jan 21, 2004·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Jul 15, 2006·Journal of Thrombosis and Haemostasis : JTH·N BovenschenA B Meijer
May 25, 2010·Haemophilia : the Official Journal of the World Federation of Hemophilia·P M W van HeldenJ Voorberg
Nov 13, 2012·Journal of Thrombosis and Haemostasis : JTH·A WroblewskaJ Voorberg
Jan 25, 2011·Journal of Thrombosis and Haemostasis : JTH·I Dienava-VerdooldB de Laat
Oct 13, 2011·British Journal of Haematology·Ankit MahendraSébastien Lacroix-Desmazes
May 9, 2014·Xenotransplantation·John M StewartMary Kearns-Jonker
Aug 15, 2006·Journal of Molecular Biology·Ulrika AndréassonMats Ohlin
Apr 26, 2014·Blood·Jan Voorberg, Henriët Meems
Aug 29, 2014·PloS One·Neda BarjestehShayan Sharif
Apr 5, 2003·Blood·Sylvie VillardClaude Granier
Dec 13, 2003·Blood·Jean Guy G GillesJean-Marie R Saint-Remy
Jan 11, 2003·The Journal of Biological Chemistry·Niels BovenschenKoen Mertens
Apr 20, 2004·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Natalya M AnanyevaEvgueni L Saenko