Humoral immune responsiveness to a defined epitope on factor VIII before and after B cell ablation with rituximab

Molecular Immunology
Christoph KesselW Kreuz

Abstract

In hemophilia A, up to 30% of patients develop neutralizing antibodies (inhibitors) to factor VIII (FVIII). Treatment of an inhibitor patient with anti-CD20 (rituximab) provided an opportunity to study the humoral immune response to the well defined and constantly administered antigen, FVIII, before therapy and after B cell repopulation. Levels of CD20(+) B cells, inhibitor titers as well as antibody titers to selected antigens and FVIII-specific IgG subclasses were monitored. Inhibitors were absent for 420 days after B cell depletion, whereas antibody titers to other monitored antigens remained constant. No changes of FVIII specific IgG subclass distribution were observed. In order to characterize specific epitopes phage displayed random peptide libraries were screened with plasma before treatment and after recurrence of inhibitors. A peptide corresponding to a dominant amino acid motif selected by phage display bound FVIII-specific IgG1 before and after anti-CD20 treatment and partially restored FVIII activity in vitro. This peptide mimics a conformational epitope in the A2 domain of factor VIII, which is still recognized after inhibitor relapse despite complete B cell depletion and long-term absence of inhibitors. Mapping of...Continue Reading

References

Mar 15, 1990·Thrombosis Research·J M Sánchez-CuencaJ A Aznar
Apr 1, 1970·The Journal of Clinical Investigation·A MorellT A Waldmann
Jun 1, 1994·The Journal of Clinical Investigation·P LollarD Scandella
Dec 31, 1997·The Journal of Biological Chemistry·I M LubinP Lollar
Feb 13, 2001·Clinical Immunology : the Official Journal of the Clinical Immunology Society·G V Gonzalez-StawinskiR D Davis
Feb 19, 2002·Immunology·Rob C Aalberse, Janine Schuurman
Dec 14, 2002·Science·Nadia L BernasconiAntonio Lanzavecchia
Jun 29, 2004·Journal of Thrombosis and Haemostasis : JTH·P Lollar
Jul 9, 2004·Scandinavian Journal of Immunology·P SzodorayM Centola
Oct 14, 2004·Haemophilia : the Official Journal of the World Federation of Hemophilia·J-M R Saint-RemyJ Oldenburg
Nov 6, 2004·Arthritis and Rheumatism·Jennifer H AnolikIñaki Sanz
Apr 19, 2005·Journal of Computational Chemistry·Andreas SchreiberUrsula Dietrich
Jan 18, 2006·Haemophilia : the Official Journal of the World Federation of Hemophilia·M CarcaoUNKNOWN Inhibitor Subcommittee of Association of Hemophilia Clinic Directors of Canada
Feb 1, 2006·Arthritis and Rheumatism·Maria J LeandroJonathan C W Edwards
Mar 23, 2006·Annual Review of Immunology·Flavius Martin, Andrew C Chan
Sep 18, 2007·Science·Dennis R Burton, Ian A Wilson
Jan 1, 1995·Haemophilia : the Official Journal of the World Federation of Hemophilia·W KreuzB Kornhuber

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Citations

Jan 28, 2009·Clinical Reviews in Allergy & Immunology·Géraldine Lavigne-LissaldeClaude Granier
May 15, 2013·PloS One·Kenneth B LewisUNKNOWN PATH (Personalized Alternative Therapies for Haemophilia) Study Investigators
Jan 5, 2014·TheScientificWorldJournal·Orish Ebere Orisakwe, Jonathan Oye Otaraku
Jul 9, 2009·Journal of Thrombosis and Haemostasis : JTH·B Waters, D Lillicrap
Aug 29, 2012·British Journal of Haematology·Donna M DiMichele
Jul 1, 2014·Haemophilia : the Official Journal of the World Federation of Hemophilia·G D MinnoC Königs
Feb 13, 2009·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Manijeh LakHassan Mansouritorghabeh
Jun 18, 2009·ChemMedChem·Christoph KesselChristoph Königs
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·D M Di Michele
Nov 26, 2010·Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering·Mohammed A GondalM S Alsalhi
Nov 20, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·J KahleC Königs

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