International SCIentinel study: Early detection can reduce risk of complications

Picture: Severe acute spinal cord injury in the area of the cervical spine. In addition to the complete loss of motor function and sensitivity, such a complete paraplegia is also accompanied by vegetative dysfunctions below the level of damage. Brain and immune organs can no longer communicate, immune function is weakened. © Charité | Marcel Kopp
Berlin, 28.06.2023
After an accident or severe injury, nerve tracts in the spinal cord may be damaged or severed. This is called paraplegia. Depending on the location of the injury, different parts of the body are affected by failures and paralysis. Researchers led by the Charité – Universitätsmedizin Berlin have now investigated the extent to which spinal cord injuries also contribute to impaired immune function. In the scientific journal Brain*, they describe, among other things, how complete paraplegia leads to immune deficiency and an increased risk of infection. These can hinder neurological recovery or even be life-threatening. Prevention, on the other hand, can reduce the risks.
Acute paraplegic patients are particularly susceptible to infections, such as respiratory or urinary tract infections. The exact cause of this was unclear for a long time. In the worst case, complications of this kind are fatal or they impair regeneration. An international research team has now systematically investigated whether the immune system is directly affected and damaged when the spinal cord is injured.
“We wanted to know whether the immune deficiency after a spinal cord injury depends on the severity and amount of damage, similar to the case with paralysis of the muscles,” says Dr Marcel Kopp, a scientist in the Experimental Neurology Department at Charité. Paraplegia is caused by a partial or complete severing of the spinal cord. Below the injury, the limbs may be paralysed and not felt. Organs or organ systems may also be affected because important nerve connections in the spinal cord are broken.
The greatest risk for people who have suffered acute paraplegia is acquired infections in the first few weeks, with subsequent sepsis, blood poisoning. Preventing them is an essential goal. Infections not only pose a risk to the patient’s survival, they also hinder the best possible recovery of neurological and motor functions. Locally targeted therapies or new preventive and immune-boosting treatments could improve rehabilitation outcomes.
Biomarkers point to risk of infection
The researchers assume that as a result of the severe injury, there is impaired communication between the brain and parts of the autonomic nervous system in the spinal cord. The lack of coordination between the nervous and immune systems eventually leads to a systemic immune deficiency. Markers in the blood that are associated with such a deficit should help to assess the susceptibility of patients to infection at an early stage and to treat them individually. So which blood changes are specific to an acute spinal cord injury? And are these changes dependent on the location and severity of the injury?
“To determine this, we examined the amount of a specific cell surface molecule on certain immune cells, the monocytes, in the blood of acutely paralysed patients. The molecule is called mHLA-DR and is a proven biomarker for assessing immune competence in intensive care patients,” explains Dr. Kopp. The results from groups of patients with different spinal cord injuries were then compared with results from patients with only vertebral body injuries and an intact spinal cord. “For severe spinal cord injuries, we were able to show that a reduced number of HLA-DR molecules per monocyte leads to a deactivation of these immune cells. Since the precursors of phagocytes are an important component of the immune defence, this marker can be used to predict susceptibility to severe infections and sepsis in critically ill people,” he says.
The higher and more severe the injury, the more pronounced the immune deficiency
Immune deficiency following spinal cord injury is also called Spinal Cord Injury-induced Immune Deficiency Syndrome (SCI-IDS). As the current study shows, it is most pronounced in patients with severe, neurologically complete spinal cord injuries above the thoracic spine. This is particularly evident in comparison with patients who have only suffered a minor injury in the lower thoracic or lumbar spine. Overall, patients with spinal cord injuries are significantly more affected than patients with a pure spinal injury without spinal cord involvement. “The spinal cord injury itself, the level of injury and the severity of the lesion are decisive factors in the development of the so-called neurogen-mediated immune deficiency,” concludes Prof. Jan Schwab, head of the multi-centre study with a total of slightly more than one hundred acutely injured patients.
The risk of life-threatening pneumonia, for example, is particularly high in patients with severe immune deficiency. In addition to the cellular immune defence, the immune memory can also be affected. This has been observed especially in spinal cord injured patients with severe and high-lying damage. Prof. Schwab concludes: “Acquired infections are a serious complication in paraplegia. Identifying particularly vulnerable patients as early as possible is therefore essential to improve their survival and independence in their later daily lives.” The studies that will now follow must show whether treatment of immunodeficiency actually leads to better outcomes in this vulnerable group of patients.
About the study
The SCIentinel study is an international prospective multicentre cohort study that analysed the specific immune profiles in the blood of 111 patients. It was supported by the German Research Foundation, the Cluster of Excellence NeuroCure, the Berlin-Brandenburg Center for Regenerative Therapies and the Wings for Life Spinal Cord Research Foundation. At the Department of Neurology and Experimental Neurology at Charité, Prof. Jan Schwab and Dr. Marcel Kopp coordinated the study, which was carried out in collaboration with other centres in Germany, Switzerland, Canada and the USA.