Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 15 December 2007, Vol. 110, No. 13, pp. 4234-4242.
Prepublished online as a Blood First Edition Paper on September 11, 2007; DOI 10.1182/blood-2007-06-096842.

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2007-06-096842v1
110/13/4234    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meeks, S. L.
Right arrow Articles by Lollar, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meeks, S. L.
Right arrow Articles by Lollar, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Next Article next article arrow

Submitted June 19, 2007
Accepted August 27, 2007

Anti-human factor VIII C2 domain antibodies in hemophilia A mice recognize a functionally complex continuous spectrum of epitopes dominated by inhibitors of factor VIII activation

Shannon L. Meeks, John F Healey, Ernest T Parker, Rachel T. Barrow, and Pete Lollar*

Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta; the Department of Pediatrics, Emory University, Atlanta, GA, United States

* Corresponding author; email: jlollar{at}emory.edu.

The diversity of factor VIII (fVIII) C2 domain antibody epitopes was investigated by competition ELISA using a panel of 56 antibodies. The overlap patterns produced five groups of monoclonal antibodies (MAbs), designated A, AB, B, BC and C, and yielded a set of 18 distinct epitopes. Group-specific loss of antigenicity was associated with mutations at the Met2199/Phe2200 phospholipid binding {beta}-hairpin (Group AB MAbs) and at Lys2227 (Group BC MAbs), which allowed orientation of the epitope structure as a continuum that covers one face of the C2 {beta}-sandwich. MAbs from Groups A, AB, and B inhibit the binding of fVIIIa to phospholipid membranes. Group BC was the most common group and displayed the highest specific fVIII inhibitor activities. MAbs in this group are Type II inhibitors that inhibit the activation of fVIII by either thrombin or factor Xa and poorly inhibit the binding of fVIII to phospholipid membranes or vWf. Group BC MAbs are epitopically and mechanistically distinct from the extensively studied Group C MAb, ESH8. These results reveal the structural and functional complexity of the anti-C2 domain antibody response and indicate that interference with fVIII activation is a major attribute of the inhibitor landscape.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 BloodHome page
S. L. Meeks, J. F. Healey, E. T. Parker, R. T. Barrow, and P. Lollar
Nonclassical anti-C2 domain antibodies are present in patients with factor VIII inhibitors
Blood, August 15, 2008; 112(4): 1151 - 1153.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020