Spinal-cord injury induces an immune deficiency in patients, study finds

COLUMBUS, Ohio – Patients recovering from a severe spinal-cord injury can develop an immune deficiency that puts them at risk of developing life-threatening infections, according to a new study by researchers at The Ohio State University Wexner Medical Center and collaborators in Germany, Switzerland and Canada. 

 

The deficiency, called spinal cord injury-induced immune deficiency syndrome, was initially identified in experimental models. The findings of this study suggest the immune deficiency also likely occurs in patients. The study of 111 patients found that monocytes, white blood cells required to fight bacterial infections, were deactivated shortly after spinal-cord injury. It also found reductions in blood levels of antibody and immunoglobulins, which are part of the body’s ‘learned’ or adaptive immunity. 

 

Furthermore, these indicators of immune deficiency were associated with the severity to spinal-cord injury. That is, they were “neurogenic,” and they add to other consequences of spinal-cord injury that also weaken the immune system such as being bed ridden, receiving anesthesia or undergoing surgery.

 

The study is reported in the journal Brain.

 

The researchers state the findings could lead to improvements in spinal-cord-injury care through staging a patient’s susceptibility to infection. This would help to identify patients who are particularly immune suppressed and to the development of new treatments to reduce infection susceptibility early on.

 

“Infections and subsequent sepsis are the main cause of death after spinal-cord injury,” said  co-corresponding author Jan Schwab, MD, PhD, the William E. Hunt & Charlotte M. Curtis Chair and a professor of neurology and neurosciences at the Ohio State College of Medicine.

 

“Our study provides evidence for an immune deficiency that sets spinal-cord injured patients up to develop infections,” said Schwab, who is also medical director of the Belford Center for Spinal Cord Injury and a Scholar of the Chronic Brain Injury Initiative at Ohio State. 

 

The findings showed that the risk of developing an immune deficiency syndrome was greatest for patients with complete, higher-level injury (fourth thoracic vertebra or above), compared with patients having incomplete, lower-level injury (fifth thoracic vertebra or lower), and compared with a reference group of patients who had vertebral fracture that did not involve the spinal cord.

 

Complete spinal-cord injury results in total loss of motor and sensory function below the level of injury; with incomplete spinal-cord injury, some function remains below the level of the injury. 

 

“Those patients with complete injuries and consequent loss of central nervous system control over immune system function displayed the highest odds for an immune deficiency,” Schwab said.

 

 

The study involved 111 patients enrolled in the international prospective multicenter cohort study known as SCIentinel study. 

 

To detect the presence and severity of immune suppression in the blood of patients, the researchers measured the levels of a cell-surface molecule called mHLA-DR on monocytes. 

 

A low number of mHLA-DR molecules is a recognized and quantifiable marker for monocyte deactivation and has been shown to predict susceptibility to sepsis in critically ill patients. 

 

 

 

“Overall, our study suggests that a neurogenic immune deficiency syndrome drives infection susceptibility in spinal-cord injury patients, and it does so in a severity-dependent manner,” Schwab said. 

 

Funding for the study was provided by Wings for Life Spinal Cord Research Foundation, the German Research Foundation (Project-ID 259373024 – TRR 167), the Elsa-Neumann-Scholarship program (Grant Number H57021), the National Institute of Disability, Independent Living and Rehabilitation Research (90SI5020), the National Institutes of Neurological Disorders-NIH (NS118200), the European Union (EU Era Net – Neuron Program, SILENCE Grant 01EW170A), the Craig H Neilsen Foundation (Grant 596764), the Wings for Life Spinal Cord Research Foundation and the William E. Hunt and Charlotte M. Curtis endowment. Jan M. Schwab is a Discovery Theme Initiative Scholar (Chronic Brain Injury) of The Ohio State University.

Other researchers involved in this study were Marcel A. Kopp, Christian Meisel, Ralf Watzlawick, Oliver Schweizerhof, Christian Blex, Tom Lübstorf, Peter Vajkoczy, Mario Cabraja, Julius Dengler, Wolfgang Ertel, Hans-Dieter Volk, Benedikt Brommer, Rick C. Hellmann, Elias Baumgartner, Julian Rind, Laura-Christin Geurtz, Ramin Raul Ossami Saidy, Harald Prüss, Ines Laginha, Vieri Failli and Ulrich Dirnagl, Charité - Universitätsmedizin Berlin, Germany; Nadine Unterwalder, Uwe Kölsch, Charité Vivantes, GmbH, Berlin, Germany; Thomas Liebscher, Erik Prilipp Andreas, Niedeggen, Kerstin Rehahn,  BG Hospital Unfallkrankenhaus Berlin, Berlin, Germany; Paolo Cinelli, Guido A. Wanner, University Hospital Zurich, Switzerland; Ulrike Grittner, Berlin Institute of Health, Berlin, Germany; Claudia Druschel, Klaus-Dieter Schaser, Universitätsklinikum Carl-Gustav Carus, Dresden, Germany; Armin Curt, University Hospital Balgrist, Zurich, Switzerland; Gertraut Lindemann, Centre for Spinal and Scoliosis Surgery, Zurich, Switzerland; Axel Ekkernkamp, BG Hospital Unfallkrankenhaus Berlin, Berlin, Germany; and Peter Martus, Eberhard Karls Universität Tübingen, Tübingen Germany. 

Media Contact: Eileen Scahill, Wexner Medical Center Media Relations, Eileen.Scahill@osumc.edu