Pathogenic antibodies are active participants in spinal cord injury

The Journal of Clinical Investigation, 2009 · DOI: 10.1172/JCI40839 · Published: October 1, 2009

Simple Explanation

Following spinal cord injury (SCI), the body's immune response, particularly B cells, can produce antibodies that hinder the healing process. These antibodies contribute to worse neurological outcomes after SCI. The study found that mice lacking B cells showed improved neurological recovery after SCI compared to normal mice. This suggests B cells play a role in the inflammatory response that impedes recovery. The presence of pathogenic antibodies in the injured spinal cord is partly due to a compromised blood-spinal cord barrier. Additionally, local antibody production within the lesion area, supported by B cell follicle-like structures, also contributes to the pathogenic outcome.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Spinal cord injury leads to a B cell response that produces pathogenic antibodies.
2
Mice lacking B cells exhibit improved neurological recovery after spinal cord injury.
3
Passive transfer of purified pathogenic antibodies into the spinal cord induces neurotoxicity.

Research Summary

The commentary discusses a study that identifies a new immunopathological mechanism arising after spinal cord injury (SCI) in mice. The study demonstrates that B cells produce pathogenic antibodies that impair lesion repair, leading to worse neurological outcomes. The authors suggest that therapies targeting B cells or blocking the effects of pathogenic antibodies may offer new immunotherapies for SCI. Potential strategies include plasmapheresis, intravenous immunoglobulin (IVIG), and B cell depletion using anti-CD20 antibodies. The commentary highlights the importance of understanding the local SCI inflammatory environment, particularly the role of the tryptophan-kynurenine pathway and IDO, in supporting B cell survival and antibody production.

Practical Implications

Novel Immunotherapies

Development of therapies targeting B cells or blocking pathogenic antibodies for SCI.

Plasmapheresis Potential

Exploring plasmapheresis to remove pathogenic autoantibodies in early SCI recovery.

IVIG Treatment

Testing intravenous immunoglobulin (IVIG) for SCI treatment due to its ability to block autoantibody binding and the complement system.

Study Limitations

1
The study was conducted in mice, and confirmation in humans is needed.
2
The mechanism by which SCI in the lower spinal cord leads to pathogenic antibody production while higher SCI can cause immune suppression requires further investigation.
3
The long-term effects and potential risks of B cell depletion therapies, especially in immunosuppressed SCI individuals, need careful consideration.

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