Immune deficiency following severe spinal cord injury

Nerve pathways in the spinal cord can be damaged or severed after an accident or serious injury, a condition known as paraplegia. Depending on where the injury is located, different parts of the body may be affected by deficits or paralysis. Researchers under the leadership of Charité – Universitätsmedizin Berlin have now studied the extent to which spinal cord injuries can also impair immune function. In an article in the journal Brain,* they describe how complete paraplegia can lead to immune deficiency and increased risk of infection. These effects can impede neurologic recovery or even be life-threatening. Prevention can help lower the risks.

Patients with acute paraplegia are especially prone to infections of areas such as the respiratory or urinary tracts. The exact cause was unclear for a long time. Complications of this kind can be fatal in the worst case, or they may adversely affect the recovery process. Now, an international team of researchers has systematically investigated the question of whether the immune system is directly affected and suffers damage in the case of a spinal cord injury.

“We wanted to know whether immune deficiency following a spinal cord injury depends on the severity and amount of damage, similar to what occurs in muscular paralysis,” says Dr. Marcel Kopp, a scholar at the Department of Experimental Neurology at Charité. Paraplegia is caused when the spinal cord is partially or entirely severed. The limbs below the injury may be paralyzed, which is accompanied by a loss of sensation. Organs or organ systems can also be affected, as important neural connections in the spinal cord are disrupted.

The biggest risk to people who have suffered acute paraplegia is infections acquired in the first few weeks, which may lead to sepsis, a type of blood poisoning. Preventing that is a key aim. After all, infections pose a risk to patient survival, but they also impede effective recovery of neurologic and motor functions. Local therapies and new preventive and immune-activating treatments could improve the results of rehabilitation.

Biomarkers point to infection risk

The researchers believe that the severe injury disrupts communication between the brain and parts of the autonomic nervous system in the spinal cord. The lack of coordination between the nervous system and the immune system ultimately produces systemic immune deficiency. Blood markers associated with this kind of deficit should help with gauging and treating patients’ individual vulnerability to infection early on. So what kinds of changes in the blood are specific to acute spinal cord injury? And do these changes depend on the position and severity of injury?

“To determine that, we studied the blood of patients with acute spinal cord injury to determine the amount of a specific molecule present on the surface of monocytes, a certain kind of immune cell. This molecule, mHLA-DR, is a proven biomarker used to assess immune competence in intensive care patients,” Kopp explains. The results from groups of patients with different injuries to the spinal cord were then compared with the results from patients who only had an injury to the vertebrae with the spinal cord still intact. “For severe spinal cord injuries, we were able to show that a reduced number of HLA-DR molecules per monocyte causes deactivation of these immune cells. Since these precursors of phagocytes are an important element of the immune defense mechanism, this marker can be used to estimate propensity to severe infection and sepsis in critically ill patients,” Kopp comments.

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

This type of condition is also known as Spinal Cord Injury-induced Immune Deficiency Syndrome (SCI-IDS). As the recent study finds, it is most pronounced in patients with severe, neurologically complete spinal cord injuries above the thoracic spine. This is especially clear in comparison to patients who have suffered less severe injuries in the area of the lower thoracic or lumbar spine. Overall, patients with spinal cord injuries are affected to a significantly greater degree than those with purely spinal column injuries not involving the spinal cord. “The spinal cord injury itself, how far up the spine it is located, and the severity of the lesion are crucial factors in the emergence of neurologically induced immune deficiency,” concludes Prof. Jan Schwab, the head of the multicenter study, which involved a little more than one hundred acutely injured patients.

Patients with severe immunodeficiency are at especially high risk of life-threatening pneumonia, for example. Cellular immune defenses are not the only things affected, either. Immunological memory can also be impaired. This was observed in particular in those with severe spinal cord injuries and injuries located farther up the spine. Schwab concludes: “Acquired infections are a serious complication in cases of spinal cord injury. It is therefore crucial to identify patients who are at special risk as early as possible in order to improve survival and independence in these patients’ later daily lives.” It will now be up to further studies to show whether treating the immune deficiency does in fact lead to better outcomes in this vulnerable patient group.

*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

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.