Does Spinal Cord Injury Pave the Way to Immune Deficiency?

Total paraplegia can induce immune deficiency and heightened infection susceptibility
Nerve routes in the spinal cord may suffer harm or severance following an incident or grave trauma, a state termed paraplegia (PEXELS)
Nerve routes in the spinal cord may suffer harm or severance following an incident or grave trauma, a state termed paraplegia (PEXELS)

Depending on the site of the injury, diverse body regions may encounter deficits or paralysis. Scientists led by Charité – Universitätsmedizin Berlin have recently investigated the magnitude of immune function impairment caused by spinal cord injuries. Within a publication in the journal Brain,* they outline how total paraplegia can induce immune deficiency and heightened infection susceptibility. Such consequences may hinder neurological recuperation or pose a mortal threat. Mitigation efforts can aid in reducing the associated hazards.

Total paraplegia can induce immune deficiency and heightened infection susceptibility (PEXELS)
Total paraplegia can induce immune deficiency and heightened infection susceptibility (PEXELS)
Individuals afflicted with sudden paraplegia are particularly susceptible to infections in regions like the respiratory or urinary tracts.
Scientists of Charité – Universitätsmedizin Berlin

The precise etiology remained elusive for an extended duration. Such complications, at their most severe, can lead to fatality, or they can impede the recuperative journey. Presently, an international consortium of researchers has meticulously explored the inquiry concerningwhether the immune system endures direct impact and sustains harm following a spinal cord injury.

"We aimed to ascertain whether immune deficiency resulting from a spinal cord injury is contingent upon the severity and extent of the damage, akin to what transpires in muscular paralysis," states Dr. Marcel Kopp, a researcher affiliated with the Department of Experimental Neurology at Charité. Paraplegia arises when the spinal cord is partially or completely severed, resulting in paralysis of the limbs below the injury and a diminished sense of sensation. Additionally, vital neural connections in the spinal cord disruption can impact organs or organ systems.

The primary peril faced by individuals with acute paraplegia lies in acquiring infections within the initial weeks, which can escalate to sepsis, a form of bloodstream infection. Preventing such infections constitutes a crucial objective. Infections not only jeopardize patient survival but also hinder the successful restoration of neurological and motor functions. Enhanced outcomes in rehabilitation could be achieved through the implementation of localized therapies, as well as novel preventive and immune-stimulating treatments.

Nerve routes in the spinal cord may suffer harm or severance following an incident or grave trauma, a state termed paraplegia (PEXELS)
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According to the researchers, they posit that the profound injury causes disruption in the communication between the brain and segments of the autonomic nervous system within the spinal cord. The resulting lack of coordination between the nervous system and the immune system ultimately gives rise to systemic immune deficiency. Biomarkers point to infection risk-By identifying blood markers associated with this type of deficit, it becomes possible to assess and address individual patients' susceptibility to infection at an early stage. Consequently, it leads to the question of what specific alterations occur in the blood due to acute spinal cord injury, and whether these changes are contingent upon the location and severity of the injury.

"To investigate this, we analyzed the blood of individuals with acute spinal cord injury to measure the levels of a specific molecule present on the surface of monocytes, a particular type of immune cell," explains Kopp. "This molecule, mHLA-DR, is a validated biomarker used to evaluate immune competence in intensive care patients." The findings obtained from patient groups with varying spinal cord injuries were then compared with those of patients who solely had an injury to the vertebrae while the spinal cord remained intact.

In the case of severe spinal cord injuries, we observed a decrease in the number of HLA-DR molecules per monocyte, resulting in the deactivation of these immune cells.
Dr. Marcel Kopp,Department of Experimental Neurology at Charité

Given that these precursor cells of phagocytes play a crucial role in the immune defense mechanism, this marker can be utilized to assess the susceptibility to severe infection and sepsis in critically ill patients."

The higher up the spine and more severe the injury is, the more pronounced the immunodeficiency

Dr. Marcel Kopp, Department of Experimental Neurology at Charité

This particular condition is also recognized as Spinal Cord Injury-induced Immune Deficiency Syndrome (SCI-IDS).

According to the recent study, SCI-IDS most prominent in individuals with severe, fully neurological spinal cord injuries above the thoracic region.
Dr. Marcel Kopp, Department of Experimental Neurology at Charité

This contrast is particularly evident when compared to patients who have experienced milder injuries in the lower thoracic or lumbar spine area. Overall, patients with spinal cord injuries are considerably more affected by SCI-IDS than those with injuries limited to the spinal column without involvement of the spinal cord. "The spinal cord injury itself, its location along the spine, and the severity of the lesion are pivotal factors contributing to the development of neurologically induced immune deficiency," concludes Prof. Jan Schwab, the lead researcher of the multicenter study, which included slightly over one hundred acutely injured patients.

Patients with severe immunodeficiency are particularly susceptible to life-threatening conditions such as pneumonia. The impact of spinal cord injuries extends beyond cellular immune defenses; it can also impair immunological memory. This effect is especially evident in individuals with severe spinal cord injuries, particularly those located higher up the spine.

Acquired infections are a significant complication in cases of spinal cord injury.
Prof. Jan Schwab, the lead researcher of the multicenter study

Therefore, early identification of patients at high risk is crucial to enhance survival and promote independence in their daily lives." Further studies will be necessary to determine whether addressing the immune deficiency indeed leads to improved outcomes in this vulnerable patient population.'

*Kopp MA et al. The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study. Brain 2023 Jun 28. doi: https://doi.org/10.1093/brain/awad092

Nerve routes in the spinal cord may suffer harm or severance following an incident or grave trauma, a state termed paraplegia (PEXELS)
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About the study
The SCIentinel study is a prospective, international, multicenter cohort study that analyzed the specific immune profiles in the blood of 111 patients. It was supported by the German Research Foundation (DFG), the NeuroCure Cluster of Excellence, the BIH Center for Regenerative Therapies (BCRT), and the Wings for Life Spinal Cord Research Foundation. Prof. Jan Schwab and Dr. Marcel Kopp coordinated the study at the Department of Neurology with Experimental Neurology at Charité. The study arose in cooperation with additional centers in Germany, Switzerland, Canada, and the United States. (MP/NW)

Nerve routes in the spinal cord may suffer harm or severance following an incident or grave trauma, a state termed paraplegia (PEXELS)
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