Data_Sheet_1_Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies.PDF

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.

脊髓损伤（Spinal cord injury, SCI）会引发长期的神经功能与全身系统异常，其中包括抗体介导的自身免疫反应，该反应已被证实与受损的功能恢复密切相关。本研究发现，在人类脊髓损伤后的亚急性期（损伤后1个月）浓度升高的自身抗体，在健康受试者体内便已存在，且其靶向的是正常脊髓中极少出现的非天然蛋白质。这类自身抗体的浓度升高是一种快速过程——损伤后5天内其水平便已升高，这一特征符合继发性免疫应答的特点，进一步佐证了其起源为天然抗体。通过蛋白质组学研究，本研究已明确：浓度升高的自身抗体靶向16种不同的神经系统与全身系统自身抗原，这些抗原与脊髓损伤后已知发生的病理变化相关，包括神经细胞骨架、代谢及骨重塑的改变。综上，结合既往研究成果，本研究结果为脊髓损伤后自身免疫反应的发生机制提供了合理解释，并鉴定出脊髓损伤病理过程中潜在的新型靶点，有待进一步深入研究。