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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., Haberland, A., Berg, S., Schulz, A., Freyse, E.J., Dahmen, C., Kage, A., Dandel, M., Vetter, R., Salzsieder, E., 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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