Lesional Antibody Synthesis and Complement Deposition Associate With De Novo Antineuronal Antibody Synthesis After Spinal Cord Injury

Neurol Neuroimmunol Neuroinﬂamm, 2023 · DOI: 10.1212/NXI.0000000000200099 · Published: May 1, 2023

Simple Explanation

This study investigates if spinal cord injury (SCI) can lead to the body producing autoantibodies that target the spinal cord and neurons. They examined blood samples from SCI patients to see if these autoantibodies were present. The research found that some SCI patients developed autoantibodies that bound to specific areas of the spinal cord and to dorsal root ganglia (DRG) neurons, which are important for sensory and motor functions. These autoantibodies were more common in patients with more severe SCI and were associated with the use of neuropathic pain medication, suggesting a link between the immune response and pain after SCI.

Study Duration

Several months

Participants

74 patients in cohort study, 27 in neuropathologic case-control study

Evidence Level

Not specified

Key Findings

1
A subpopulation of SCI patients (16%) developed autoantibodies that bind to spinal cord epitopes and DRG neurons, while these were absent in vertebral fracture controls.
2
The autoantibody binding in the spinal cord was characteristically detected in the substantia gelatinosa, a region involved in sensory-motor integration and pain processing.
3
Neuropathologic analysis revealed lesional spinal infiltration of B cells and plasma cells in SCI patients, with IgG and IgM antibody synthesis colocalizing to areas of activated complement deposition.

Research Summary

The study provides evidence for de novo post-traumatic antibody synthesis at the spinal cord lesion site and emerging antibody-mediated autoimmunity after human SCI, directed against spinal cord and DRG neuronal surface epitopes. Neuropathologic analysis confirmed B cell infiltration followed by the emergence of plasma cells, which demonstrate IgM and IgG antibody syntheses. Regions of IgG and IgM syntheses colocalize with areas of complement activation. The development of autoimmunity depends on the severity and lesion level of SCI, and non-neurogenic factors such as increased Factor XII levels and CD8/CD3 ratios may also contribute.

Practical Implications

Diagnostic potential

The identification of specific autoantibodies could aid in diagnosing paratraumatic CNS autoimmune syndromes.

Therapeutic targets

Understanding the role of B cells and complement activation could lead to new therapeutic strategies to modulate the immune response after SCI.

Personalized medicine

Identifying patient subpopulations with a higher risk of developing autoimmunity could allow for tailored interventions and monitoring.

Study Limitations

1
Serum samples are not accompanied by CSF samples.
2
The specific target antigen of the autoantibodies is not yet known.
3
Further studies are needed to identify specific cognate surface epitopes of neurons, synapses, and glia.

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