Complex Autoantibody Responses Occur Following Moderate to Severe Traumatic Brain Injury
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Abstract
Most of the variation in outcome following severe traumatic brain injury (TBI) remains unexplained by currently recognised prognostic factors. Neuroinflammation may account for some of this difference. We hypothesised that TBI generated variable autoantibody responses between individuals that would contribute to outcome.
We developed a custom protein microarray to detect autoantibodies to both central nervous system and systemic antigens in serum from the acute-phase (the first seven days), late (6-12 months) and long-term (6-13 years) intervals after TBI in human patients.
We identified two distinct patterns of immune response to TBI. The first was a broad response to the majority of antigens tested, predominantly IgM-mediated in the acute-phase, then IgG-dominant at late and long-term time-points. The second was responses to specific antigens, most frequently myelin-associated glycopeptide (MAG), which persisted for several months post-TBI but then subsequently resolved.
Exploratory analyses suggested that patients with a greater acute IgM response experienced worse outcomes than predicted from current known risk factors, suggesting a direct or indirect role in worsening outcome. Furthermore, late persistence of anti-MAG IgM autoantibodies correlated with raised serum neurofilament light concentrations at these time points, suggesting an association with ongoing neurodegeneration over the first year post-injury.
Our results show that autoantibody production occurs in some individuals following TBI, can persist for many years, and is associated with worse patient outcome. The complexity of responses mean that conventional approaches based on measuring responses to single antigenic targets may be misleading.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
1550-6606
Volume Title
Publisher
Publisher DOI
Rights
Sponsorship
Addenbrooke's Charitable Trust (ACT) (25/16 A)
Intensive Care Society (Unknown)
Academy of Medical Sciences (unknown)
Medical Research Council (MR/R005036/1)
Medical Research Council (G0802251)
Royal College of Surgeons of England (2016/2017)
Wellcome Trust (105924/Z/14/Z)
Wellcome Trust (105924/Z/14/A)
Wellcome Trust (105924/Z/14/Z)
Wellcome Trust (105924/Z/14/A)
Medical Research Council (G0802251/1)