Spinal Cord Injury Patients at Higher Risk for Immune Deficiency

Summary: Patients recovering from severe spinal cord injuries are more susceptible to immune deficiencies.

Such deficiencies, known as spinal cord injury-induced immune deficiency syndrome, may expose patients to life-threatening infections. This immune deficiency is closely tied to the severity of the spinal cord injury and can undermine the immune system further.

The research could pave the way for better patient care by identifying highly immune-suppressed patients and devising new treatments to curb infection susceptibility.

Key Facts:

  1. Patients recovering from severe spinal cord injuries can develop an immune deficiency, increasing their risk of life-threatening infections.
  2. The severity of the spinal cord injury directly correlates with the extent of the immune deficiency, leading to further weakening of the immune system.
  3. The findings could contribute to the enhancement of spinal cord injury care by identifying patients with pronounced immune suppression and creating treatments to reduce susceptibility to infections.

Source: Ohio State University

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 study is reported in the journal Brain.

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.

This shows the outline of a person with the spinal cord highlighted.
Furthermore, these indicators of immune deficiency were associated with the severity to spinal-cord injury. Credit: Neuroscience News

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 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, Ph.D., 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 multi-center 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.

Key findings include:

  • Patients with high complete injury had the highest burden of pulmonary and urinary tract infections, including recurrent infections;
  • Patients with infections had mHLA-DR levels below the reference value for “immune suppression” within two weeks after injury;
  • Patients with early infection (in the first or second week) had especially low mHLA-DR values in the range of “borderline immunoparalysis” already at 15 hours after injury;
  • A drop in immunoglobulin (IgG and IgA) levels after spinal-cord injury suggested depressed humoral immunity as well. This was most pronounced in high completely injured patients;
  • Both cellular and non-cellular immune defense mechanisms were compromised in spinal cord injury patients and associate with early onset of infections.

“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.

About this spinal cord injury and neurology research news

Author: Jan Schwab
Source: Ohio State University
Contact: Jan Schwab – Ohio State University
Image: The image is credited to Neuroscience News

Original Research: Open access.
The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study” by Jan Schwab et al. Brain


The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections.

The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI.

The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures.

Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters.

Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. 

Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of −0.43 (95% CI: −0.66; −0.20) at 14 days.

Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [−0.27 (95% CI: −0.45; −0.10)] and immunoglobulin A [−0.25 (95% CI: −0.49; −0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery.

Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

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