Confirmed: Spinal Cord Injury Can Suppress Immune Function

Prior observations that patients suffering spinal cord injuries are prone to develop infections may now have an explanation.

Biomarkers of immune activity were depressed for at least 2 weeks following spinal cord injury (SCI), researchers found in a prospective study of 70 SCI patients and 41 controls with vertebral fractures but intact spinal cords, according to Jan M. Schwab, MD, PhD, of Ohio State University in Columbus, and colleagues.

Moreover, the degree of immune suppression correlated with the severity and location of the SCIs, the group reported in Brain.

“Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR [monocytic human leukocyte antigen-DR] expression and relative hypogammaglobulinemia (combined cellular and humoral immune deficiency),” Schwab and colleagues concluded.

Explanations for the increased infection risk postulating autonomic dysregulation and immunosuppression had been advanced before, the group noted. However, these mechanisms hadn’t been quantified, and how antibody function might be affected had not been addressed.

“To determine both, it is necessary to disentangle a neurogenic injury level and severity-dependent SCI-IDS [immune deficiency syndrome] from an unspecific, trauma-related post-aggression syndrome mirroring a generalized stress response,” Schwab and colleagues explained.

To do so, the group commenced the new study, called SCIentinel, nearly 15 years ago with the aim of tracking SCI patients stratified by injury location and severity, along with a control group having non-SCI traumatic injuries. Patients were enrolled at seven centers in Germany, Switzerland, and Canada. For purposes of analysis, SCI location was defined as either T4 and above (high SCI, n=41) or T5 and below (low SCI, n=29); severity was stratified as complete (n=36) or incomplete (n=34). Viewed as a 2×2 matrix, the four SCI categories had from 13 to 21 patients, plus 41 non-SCI controls.

The main outcome of interest was expression of monocytic HLA-DR — also known as major histocompatibility complex II — as assessed periodically during the first 2 weeks after injury and again at week 10. Other measurements included leukocyte subpopulation counts and serum immunoglobulin levels, as well as clinical infections.

Monocytic HLA-DR expression was numerically highest at every time point in the control group. The lowest was in the group with high and complete SCI, followed by incomplete high SCI, complete low SCI, and incomplete low SCI.

As for timing, this pattern was most prominent in the first few days after injury. By day 14, the gaps had shrunk somewhat and HLA-DR expression had increased from the previous assessments, and the differences between groups almost vanished at week 10.

Neutrophil and monocyte counts did not differ markedly between groups, although a downward trend over time was noted. CD3+ T-cell and lymphocyte counts increased and were similar in the five groups; CD19+ B-cell counts remained largely unchanged. Yet, immunoglobulin G (IgG) titers appeared to be decreased in the SCI patients relative to controls throughout the study, most especially in those with complete SCI. A similar pattern, but less pronounced, was seen for IgA and IgM.

SCI patients had markedly higher infection rates, which followed the same pattern as HLA-DR expression but in reverse: highest in patients with complete high SCI, followed by incomplete high SCI, low complete SCI, low incomplete SCI, and finally the controls. Only five infections were seen in controls, versus 42 among patients with high complete SCI. Most common were upper respiratory and urinary tract infections.

Schwab and colleagues indicated that the findings have clinical relevance. “The identification of a neurogenic, SCI severity and lesion level-dependent SCI-IDS developing independent of demographic baseline criteria provides a tangible framework to tackle limitations in current SCI care,” they wrote.

In particular, they continued, the study points the way toward:

• A staging system for post-SCI infection risk
• Triage protocols for post-SCI immunosuppression
• Targets for new immunoprotective therapies

Limitations to the study included missing data for some patients immediately after injury and at the 10-week evaluation, although the investigators said they expected this and accounted for it in their enrollment targets.

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