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A COVALENT REACTIVE ANTIGEN ANALOG TO FACTOR VIII REDUCES ANTIBODY PRODUCTION IN MEMORY B CELLS AFTER RE-STIMULATION WITH FVIII
Abstract number: O-M-063
Smith1 K.C., Planque1 S.A., Nishiyama1 Y., Escobar2 M.A., Paul1 S.
11Pathology and Laboratory Medicine 22Medicine and Pediatrics and The Gulf States Hemophilia Center, University of Texas Health Science Center, Houston, United States
How-to-cite Smith KC, Planque SA, Nishiyama Y, Escobar MA, Paul S. A COVALENT REACTIVE ANTIGEN ANALOG TO FACTOR VIII REDUCES ANTIBODY PRODUCTION IN MEMORY B CELLS AFTER RE-STIMULATION WITH FVIII. J Thromb Haemost 2007; 5 Supplement 2: O-M-063
Abstract
Introduction: B lymphocytes producing high titer antibodies (Abs) to factor VIII (FVIII) are of major concern in the treatment of bleeding episodes in a subpopulation of patients with hemophilia A. We hypothesize that covalent reactive FVIII antigen analogs (FVIII-CRAs) can induce tolerance in an antigen-specific manner by permanent engagement of the BCRs.
Methods: To accomplish this, we created a FVIII-CRA by derivitizing FVIII lysine side chains with phosphonate diester groups. We demonstrated that the FVIII-CRA covalently bound to polyclonal IgG Abs isolated from hemophilia A patients. Hence, we also predicted that the FVIII-CRA could also irreversibly bind to enzyme-like nucleophilic residues located within the BCR
Results: The number of total viable antibody forming cells (ASC) produced in response to re-stimulation with FVIII-CRA were significantly decreased (avg of 111 SFC vs 36 SFC, p = 0.03). These results suggested that FVIII-CRA might have a tolerogenic effect on memory B lymphocytes. To confirm this, we pre-treated CD138- splenocytes with FVIII-CRA, and then added a stimulatory dose of FVIII to the cultures. Pre-treatment with FVIII-CRA resulted in a significant 17-fold decrease in the number of ASC produced in response to FVIII when compared to the response generated after OVA pretreatment.
Conclusions: These results suggest that FVIII-CRA may represent a viable means to induce antigen-specific tolerance in hemophilia.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
Session Details
| Date: |
01/08/2007
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| Time: |
00:00-00:00
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| Session name: |
XXIst ISTH Congress |
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| Location: |
Oxford, UK |
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