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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02033

Encoding the Sequence of Specific Autoantibodies Against beta-Amyloid and alpha-Synuclein in Neurodegenerative Diseases

 Alexandra Albus1, 2, 3*,  Marit Jördens3,  Moritz Möller3 and Richard Dodel1, 2, 3
  • 1University of Duisburg-Essen, Germany
  • 2Essen University Hospital, Germany
  • 3University of Marburg, Germany

There is no effective disease-modifying therapy for Alzheimer’s and Parkinson’s Disease. As pathological hallmarks, the specific proteins Amyloid-β and α-Synuclein aggregate, deposit and destabilize neurons, which lead to their degeneration. In the context of a potential immunization strategy for these diseases, naturally occurring autoantibodies could play a crucial role due to their ability to inhibit protein aggregation and to mediate their phagocytosis. We developed a procedure to extract the genetic information of these Amyloid-β- and α-Synuclein- specific naturally occurring autoantibodies for future passive immunization strategies. We performed FACS-based single-cell sorts from healthy whole-blood donations and performed single-cell RT-PCR studies to duplicate the coding sequences of antigen-binding regions of each antibody-secreting B1 cell. Sequences were further analyzed to determine the CDR sequences and the germline expression. Thereby, only low percentages of B1 cells were Amyloid-β+/α-Synuclein+. After cell sorting the variable regions of full IgGs were sequenced. Thereby, the sequence analysis demonstrated a preferred usage of IGVH3 and IGKV1.
The study we present here describes a way to extract and duplicate the sequence information of autoantibodies based on single blood donations and to produce a recombinant antibody pool for a potential passive immunization against neurodegenerative diseases. We sorted a small pool of CD20+ CD27+ CD43+ CD69- IgG+ and Aβ+/α-Syn+ B cells.

Keywords: B1 cell, Naturally occurring autoantibodies, Alzheimer's disease, Parkinson's disease, Single cell RT-PCR, passive immunization strategy

Received: 01 Mar 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Albus, Jördens, Möller and Dodel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ms. Alexandra Albus, University of Duisburg-Essen, Duisburg, Germany,