The First Aptamer-Apheresis Column Specifically for Clearing Blood of β1-Receptor Autoantibodies: A Successful Proof of Principle Using Autoantibody-Positive SHR Rats

Background: Application of immunoapheresis to eliminate pathogenic autoantibodies targeting the second extracellular loop of the β1-receptor (β1-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 spe...

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Bibliographic Details
Published in:Circulation Journal 2012, Vol.76(10), pp.2449-2455
Main Authors: Wallukat, Gerd, Haberland, Annekathrin, Berg, Sabine, Schulz, Angela, Freyse, Ernst-Joachim, Dahmen, Claudia, Kage, Andreas, Dandel, Michael, Vetter, Roland, Salzsieder, Eckhard, Kreutz, Reinhold, Schimke, Ingolf
Format: Article
Language:English
Subjects:
Apheresis
Aptamer
Autoantibody
Dilated cardiomyopathy
Immunoadsorption
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Summary:Background: Application of immunoapheresis to eliminate pathogenic autoantibodies targeting the second extracellular loop of the β1-receptor (β1-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 β1-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 β1-AABs from rat’s blood. Methods and Results: An apheresis column was designed containing the β1-AAB-targeting-aptamer coupled to sepharose. As tested in vitro, this column (1) binds β1-AABs highly specifically without marked interference with common IgGs, (2) has a capacity for clearing of approximately 1L of β1-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 β1-AABs and muscarinic 2-receptor autoantibodies (M2-AABs), only β1-AABs were removed. In a follow-up of 9 weeks, recurrence of β1-AABs in the blood of SHR could not be detected. Conclusions: For the first time, a newly designed apheresis column with a β1-AAB specific aptamer as a binder was successfully used to eliminate β1-AABs from SHR blood.  (Circ J 2012; 76: 2449–2455)
ISSN:1346-9843
1347-4820
DOI:10.1253/circj.CJ-12-0212