The first aptamer-apheresis column specifically for clearing blood of β1-receptor autoantibodies.

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.