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Complex Autoantibody Responses Occur Following Moderate to Severe Traumatic Brain Injury

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Outtrim, joanne 
Mousa, hani 
Hutchinson, pete 


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.



Adult, Autoantibodies, Brain Injuries, Traumatic, Female, Humans, Male, Middle Aged, Young Adult

Journal Title

Journal of Immunology

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American Association of Immunologists


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Freemasons' Grand Charity (unknown)
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)
EJN, AH, AJC, PJH and DKM are supported by the Medical Research Council (UK) within the framework of ERA-NET NEURON. ERZ is supported by the Ministero della Salute (Italy) within the framework of ERA-NET NEURON. DKM is supported by an NIHR Senior Investigator Award and European Union 7th Framework program (EC grant 602150). EJN is supported by the Intensive Care Society Young Investigator Award, Addenbrookes Charitable Trust Cambridge Clinical Research Fellowship and NIHR Brain Injury Healthcare Technology Co-operative Seedcorn funding. EPT acknowledges funding from Region Stockholm (ALF), the Swedish Brain Foundation (Hjärnfonden) and the Swedish Society for Medical Research (Svenska Sällskapet för Medicinsk Forskning). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), Centrum för Idrottsforskning (#P2019-0198), and the UK Dementia Research Institute at UCL. PJH is funded by the NIHR (Research Professorship and Cambridge BRC) and Royal College of Surgeons of England. JJ is funded by the Wellcome Trust (RG79413). VFJN is funded by an Academy of Medical Sciences / The Health Foundation Clinician Scientist Fellowship. HSM is supported by the Cambridge Trust and the Rosetrees Trust
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