April 6, 2023

COLUMBUS, Ohio – A subgroup of patients recovering from severe spinal-cord injury can develop an autoimmune response directed against spinal cord proteins that may associate with pain development according to a new study by researchers at The Ohio State University Wexner Medical Center and College of Medicine, along with collaborators in Germany, Austria, Italy, Canada and Switzerland. 
The researchers found that, after spinal-cord injury, the immune system of some patients produces antibodies that bind to the spinal cord and living neurons. The researchers state that such autoantibodies could lead to the development pain or even interfere with the response to rehabilitation. The findings could lead to new treatments for spinal-cord injury patients who have certain antibody profiles.
The researchers published their findings in the journal Neurology: Neuroimmunology & Neuroinflammation, a journal published by the American Academy of Neurology (AAN).
Jan Schwab_BRT Lab_sized“To our knowledge, this is the first study to demonstrate that, after spinal-cord injury, patients may increasingly develop autoantibodies that bind to the spinal cord and to the surface of neurons,” said corresponding author Dr. Jan Schwab, the William E. Hunt & Charlotte M. Curtis Chair and a professor of neurology and neurosciences at Ohio State. 
“As such, our findings indicate that antibody-mediated autoimmune responses may emerge in some patients about three weeks after spinal-cord injury. So far, we know about antibody-mediated autoimmune syndromes developing in patients with cancer, but that it can also occur in patients after spinal cord injury is striking” said Schwab, who is also medical director of the Belford Center for Spinal Cord Injury and a Scholar of the Chronic Brain Injury Initiative at Ohio State.
The study by Schwab and Dr. Romana Hoeftberger, a Professor of Neuropathology at the Medical University in Vienna (Austria), applied and extended diagnostic methods which were earlier established to detect autoimmune diseases of the brain, such as autoimmune encephalitis. “Here, the ability to become able to diagnose patients with autoimmune encephalitis was crucial. After reaching a diagnosis, these patients can now be successfully treated, which was not possible 15 years ago. In analogy, extending this clinically validated toolbox enabled us to reveal novel autoimmune signatures after spinal cord injury, as first and necessary step,” Schwab noted. 
How the study was done
Schwab and his collaborators compared blood-serum antibodies from patients with severe (motor complete and motor incomplete) spinal cord injuries and from control patients over time. The capacity of antibodies to recognize and bind to spinal cord tissue proteins as well as living dorsal root ganglia neurons was tested in a blinded manner.
In addition, the researchers examined archival human spinal tissue samples at time points ranging from the time of injury to several months later. They looked for B- and Plasma cells as cellular origin of the antibody synthesis at the lesion site in spinal-cord injury compared to unaltered control cord tissue. 
Key findings included:
  • Robust and emerging autoantibody binding was restricted to only a subpopulation (16%) of spinal-cord injury patients; it was absent in controls. 
  • Autoantibody binding was detected mainly in a specific region of the spinal cord involved in sensory-motor integration (i.e., the substantia gelatinosa). 
  • Autoantibody binding was associated with patients who required neuropathic pain medication. 
  • The study of archival spinal-tissue lesions showed B-cell infiltration in 27% of the spinal-cord injury patients, the presence of plasma cells in 9%, synthesizing both IgG and IgM antibodies in areas of activated complement deposition. Antibody synthesis in an area of complement deposition if self-sufficient mechanism to propagate cell death. 
  • Analysis of cerebral spinal fluid from an additional single patient demonstrated IgM antibody synthesis with late re-opening of the blood spinal cord barrier.
“Overall, our study revealed a new and unexpected autoimmune signature that affects a subpopulation of patients after spinal-cord injury and qualifies as modifiable, potential mechanism to reduce pain and improve quality of life in spinal cord injured patients,” Schwab said. 
Funding for this study was provided by the Belford Family Charitable Fund, the National Institutes of Health (NS118200, NS099532, NS083942, NS111582), the National Institute of Disability, Independent Living and Rehabilitation Research (90SI5020), the Craig H. Neilsen Foundation (596764), the William E. Hunt and Charlotte M. Curtis Endowment, the Ray W. Poppleton Endowment, the European Union (SILENCE Grant 01EW170A), the Austrian Science Funds (FWF, project I3334-B27, SILENCE; I4685-B, SYNABS; DOC 33-B27) and the Wings for Life Spinal Cord Research Foundation (WfL-DE-006/12, WfL-DE-16/16, WfL17-DE-11/20) and the Else Kröner-Fresenius-Stiftung (EKFS 2012_A32).
Other researchers involved in this study were Phillip Popovich, The Ohio State University; Marcel A Kopp, Thomas Liebscher, Tom Lübstorf, Blex Christian,  Leonarda Serdani-Neuhaus, Ulrich Dirnagl, Harald Prüss, Charité, Universitätsmedizin Berlin, Germany; Carmen Haider, Tobias Zrzavy, Verena Endmayr, Gerda Ricken, Helmut Kubista, Thomas Haider, Hans Lassmann, Romana Höftberger, Medical University of Vienna, Austria; Armin Curt, Balgrist University Hospital, Zurich, Switzerland; Paolo Cinelli, University Hospital Zürich, Switzerland; Giorgio Scivoletto, IRCCS Fondazione S. Lucia, Rome, Italy; Michael G. Fehlings, University of Toronto; Caroline May, Annika Guntermann, Katrin Marcus, Ruhr-University Bochum, Bochum, Germany; Christian Meisel, Institute of Medical Immunology, Charité - Berlin, Germany; Peter Martus, Eberhard Karls, Universität Tübingen, Tübingen Germany.
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Media Contact: Eileen Scahill, Wexner Medical Center Media Relations, Eileen.Scahill@osumc.edu



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