The SCIentinel-prolong trial – deciphering humoral autoimmunity as a basis for patient specific immunotherapy
Funded in: 2016, 2017, 2018
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Problem: Elevated autoantibodies in blood samples of SCI patients
Target: Maladaptive immune response after SCI
Goal: Evaluation and definition of autoimmune responses after SCI and the link to clinical complications and to the functional outcome
Introduction: A maladaptive systemic immune response occurs early after spinal cord injury (SCI) and is characterized by i) an immune reaction against neuronal structures and ii) an immune deficiency. Both, autoimmunity and infections aggravated by immune deficiency are able to modify the patients’ outcome and may account for an impaired recovery of lost neurological function after SCI.
Problem statement: In a preparatory study we identified 108 differentially elevated autoantibodies in blood samples of SCI patients compared to a control group of patients with a vertebral fracture without SCI. However, it is not yet clear whether those autoantibodies are newly emerging after SCI and directed against the central nervous system. Here, we address three main questions: i) Is there a developing autoimmunity against central and peripheral nervous system proteins after SCI? ii) Do infections promote autoimmunity? iii) Are the targets of the autoantibodies functionally relevant?
Methods: The SCIentinel-prolong study is the first multinational trial to prospectively investigate for signs and impact of autoimmunity on neurological outcome up to one year after SCI. We systematically screen blood and cerebrospinal fluid samples from the first week up to six months after injury for autoantibodies against approximately 10,000 proteins comparing age and gender-matched pairs of SCI and control patients.
Expected results: The identified autoantibody profiles will serve for an in depth evaluation and definition of autoimmune responses after SCI. Furthermore, the autoantibody profiles can be linked to clinical complications and to the functional outcome up to one year after SCI. This enables determining trigger factors for autoimmunity such as infections and the impact of autoimmunity on the rehabilitation.
Potential application: To characterize SCI patients by the occurrence and severity of autoimmunity allows for definition of patient subgroups as a basis for the development of new individualized treatment concepts for the prevention of secondary damage after SCI.
This work aims to help acute SCI patients by unravelling autoimmunity after SCI as a contributor to secondary damage targetable by specific immune therapies.