Author ORCID Identifier


Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation


Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Pramod K. Dash, PhD

Committee Member

Jeffrey K. Actor, PhD

Committee Member

Claire E. Hulsebosch, PhD

Committee Member

J. William Lindsey, MD

Committee Member

Jack C. Waymire, PhD



Approximately 17,500 spinal cord injuries (SCI) occur yearly in the U.S. causing considerable morbidity and mortality. Neuropathic pain (NP) ensues in 40-70% of SCI. An autoimmune response resulting from disruption of the blood-spinal cord-barrier may be a contributor to NP. However, the relationship between autoantibodies and NP after SCI in humans has not been thoroughly characterized nor have autoantigens been identified. Glial fibrillary acidic protein (GFAP) and collapsin response mediator protein2 (CRMP2) were identified as candidate autoantigens. The hypothesis is that proteins from the injured spinal cord released by SCI trigger autoantibody production which can lead to the development of NP.


The presence of autoantibodies to GFAP (GFAPab) and CRMP2 (CRMP2ab) and their correlation to the development of NP was evaluated. GFAPab was present in 21 of 38 (55%) acute SCI, 34 of 80 (43%) chronic SCI. CRMP2ab was present in 8/35 (23%) acute SCI patient plasma samples. Complement C3 and C5 were elevated in acute SCI. Peak autoantibody levels were detected at 16±7 days post injury. The peak plasma GFAPab levels were higher in patients that subsequently developed NP versus those who did not (T=219, p=0.02). Receiver operator characteristic curve analysis shows that plasma GFAPab levels had an area under the curve of 0.71 (95% CI, 0.53-0.89 p=0.03) for the discrimination of patients that developed NP within 6 months after injury. Patients with GFAPab and/or CRMP2ab had a 9.5 times increased odds of developing NP.


Results show that SCI triggers an autoimmune response leading to production of autoantibodies. The 16±7 day level of GFAPab post-SCI is a predictor of the development of NP. The levels of GFAPab returned to levels found in healthy volunteers by 96±54 days post-injury. A panel of GFAPab and CRMP2ab showed 9.5 times increased odds of developing NP (95% CI, 2.08-43.50, p=0.006). Future studies will examine the possibility that other autoantibodies contribute to the development of NP. Measuring GFAPab and CRMP2ab post-SCI may help identify patients at risk for subsequently developing NP. A reduction of GFAPab and/or CRMP2ab in the acute stages of injury may decrease the likelihood for developing NP.


spinal cord injury, autoantibodies, GFAP, CRMP2, complement



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