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The first aptamer-apheresis column specifically for clearing blood of beta1-receptor autoantibodies : a successful proof of principle using autoantibody-positive SHR rats

Item Type:Article
Title:The first aptamer-apheresis column specifically for clearing blood of beta1-receptor autoantibodies : a successful proof of principle using autoantibody-positive SHR rats
Creators Name:Wallukat, G. and Haberland, A. and Berg, S. and Schulz, A. and Freyse, E.J. and Dahmen, C. and Kage, A. and Dandel, M. and Vetter, R. and Salzsieder, E. and Kreutz, R. and Schimke, I.
Abstract:Background: Application of immunoapheresis to eliminate pathogenic autoantibodies targeting the second extracellular loop of the beta1-receptor (beta1-AABs) is currently investigated in patients with cardiomyopathy. Aptamers (single short DNA or RNA strands) are a new class of molecules that bind to a specific target molecule. This property qualifies aptamers for potential use in the apheresis technique. We recently identified an aptamer that specifically binds to beta1-AABs, so in the present study we tested whether this aptamer could be used as a binder to prepare an apheresis column suitable for clearing beta1-AABs from rat's blood. Methods and Results: An apheresis column was designed containing the beta1-AAB-targeting-aptamer coupled to sepharose. As tested in vitro, this column (1) binds beta1-AABs highly specifically without marked interference with common IgGs, (2) has a capacity for clearing of approximately 1L of beta1-AAB-positive serum and (3) can be completely regenerated for subsequent use. Using the column for extracorporeal apheresis of spontaneously hypertensive rats (SHR) positive for both beta1-AABs and muscarinic 2-receptor autoantibodies (M2-AABs), only beta1-AABs were removed. In a follow-up of 9 weeks, recurrence of beta1-AABs in the blood of SHR could not be detected. Conclusions: For the first time, a newly designed apheresis column with a beta1-AAB specific aptamer as a binder was successfully used to eliminate beta1-AABs from SHR blood.
Keywords:Apheresis, Aptamer, Autoantibody, Dilated Cardiomyopathy, Immunoadsorption, Animals, Rabbits, Rats
Source:Circulation Journal
ISSN:1346-9843
Publisher:Japanese Circulation Society
Volume:76
Number:10
Page Range:2449-2455
Date:25 September 2012
Official Publication:https://doi.org/10.1253/circj.CJ-12-0212
PubMed:View item in PubMed

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