Abstract
Spinal cord injury (SCI) results in long-term neurological and systemic consequences, including antibody-mediated autoimmunity, which has been related to impaired functional recovery. Here we show that autoantibodies that increase at the subacute phase of human SCI, 1 month after lesion, are already present in healthy subjects and directed against non-native proteins rarely present in the normal spinal cord. The increase of these autoantibodies is a fast phenomenon–their levels are already elevated before 5 days after lesion–characteristic of secondary immune responses, further supporting their origin as natural antibodies. By proteomics studies we have identified that the increased autoantibodies are directed against 16 different nervous system and systemic self-antigens related to changes known to occur after SCI, including alterations in neural cell cytoskeleton, metabolism and bone remodeling. Overall, in the context of previous studies, our results offer an explanation to why autoimmunity develops after SCI and identify novel targets involved in SCI pathology that warrant further investigation.
Highlights
Spinal cord injury (SCI) results in neurological and systemic alterations that dramatically interfere with patient quality of life
To explore whether the increased serum IgG after SCI could be related to higher levels of autoantibodies (AAbs), we tested the immunoreactivity of sera samples IgG against rat spinal cord tissue
We analyzed by western blot the binding of serum IgGs to proteins isolated from spinal cords of intact and injured rats at 1 and 28 days after lesion (Figure 1M)
Summary
Spinal cord injury (SCI) results in neurological and systemic alterations that dramatically interfere with patient quality of life. Several factors contributing to SCI pathology have been proposed in an attempt to identify novel targets for therapeutic intervention One of these are autoantibodies (AAb) against central nervous system antigens, which are elevated in SCI patients and are pathogenic in rodents [1,2,3,4,5]. SCI induces B cells to proliferate and differentiate into immunoglobulin (Ig) G secreting B cells, which results in increased levels of IgG in peripheral blood [3]. Injecting these circulating IgG into the spinal cord of intact animals induces necrosis, inflammation and motor impairment [5]. The complete repertoire of AAb specificities induced after SCI remains unknown because most studies have been done by selecting the antigenic determinants to be tested “a priori,” not by unguided discovery methods
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