Aging

Immune System

Although the immune system is affected by a number of factors, including nutritional status, stress, exercise, neuroendocrine change, and disease, there is consensus that immune functioning undergoes some age-related declines (Miller 1996; Burns & Leventhal 2000; Rabin 2000). There is limited evidence on the effects of SCI on the immune system with aging, but several studies (i.e., Lyons 1987; Nash 1994; Kliesch et al. 1996; Campagnolo et al. 1999; Cruse et al. 2000) suggest deficits in immune functioning. Hence, there is greater likelihood of immune impairment in the aging SCI population compared to the non-disabled population (Charlifue & Lammertse 2002).

In this section, 1 longitudinal study and 4 cross-sectional studies on the immune system after SCI are reviewed.

Author Year; Country
Score
Research Design
Total Sample Size		 Methods Outcome

Zajarias-Fainsod et al. 2012; Mexico
Prospective controlled trial
Level 2
N SCI=12
N controls=18

 Population: 12 SCI participants (8M 4F), >10 YPI; mean (SD) age in yrs: 32(5), range 22-46; mean (SD) YPI: 19.55 (8.4), range 12-37; Level of injury: 41.66% cervical, 58.34% thoracic; AIS scale: 50% A, 50% B. 18 age-matched healthy blood donors; mean (SD) age 33(6) yrs.
Methodology: Blood samples were drawn through standard venipuncture and lymphocyte proliferation and antibody titers against myelin basic protein (MBP).
Outcome Measures:  lymphocyte proliferation (colorimetric-BrdU ELISA assay), and antibody titers against MBP (ELISA Human IgG MBP-specific assay).
  1. SCI patients presented a significant auto-reactive immune response as shown by T-cell proliferation against MBP compared to AB controls.
  2. The authors suggest that this could indicate that immune cells are expanding tissue damage after the injury or alternatively, promoting neuroprotection and regeneration.

Frisbie 2010; USA
Level 3
Case-control
Level 3
N=322

 Population: 322 SCI participants (318M 4F); had follow up service for SCI with scheduled annual checkups between 1998 and 2007.
Methodology: Cohort was divided into two groups: surviving and deceased through 2008.
Outcome Measures: Prevalence rates of anemia (AN), severe anemia (SAN) and hypoalbuminemia (HA) which might serve as markers for infection.
  1. 72% of surviving participants experienced AN during survey period.
  2. 99% of deceased participants experienced AN.
  3. SAN or HA also higher in deceased (54.2% vs. 28.0% and 61.4% vs. 28.5%).
  4. Number of survey years positive for AN, SAN, or HA higher in deceased (82.7%, 18.0%, 22.2%) vs. survivor (33.7%, 6.0%, 6.4%).
  5. SAN and HA occurred together in same survey year 78% of the times.

Furlan et al. 2006; Canada
Case-control
Level 3
N SCI=21
N controls=11

 Population: 21 participants with cervical SCI, ages 17-83 yrs, AIS A-D. 11 males and females with spine trauma, ages 18-75 yrs, AIS E as controls.
Methodology: Consecutive individuals with acute C-spine trauma from 1998-2000 were reviewed.
Outcome Measures: Blood hemoglobin concentration, leukocyte, lymphocyte and platelet count within first week of trauma.
  1. With age controlled, SCI individuals showed a significantly higher frequency for decreased hemoglobin concentration, leukocytosis, lymphopenia, and thrombocytopenia than controls within the first week post-trauma.
  2. SCI had significantly higher leukocyte count and significantly lower blood lymphocyte count than controls.
  3. Males with SCI had significantly lower hemoglobin concentration than male controls, but no differences detected between females.

Campagnolo et al. 1999; USA
Prospective controlled trial
Level 2
N SCI=18
N controls=18

 Population: 18 SCI participants (11M 7F); for persons with tetraplegia, mean age 29 (19-51 yrs), mean YPI 56.6 months; for persons with paraplegia, mean age 32.6 (21-50 yrs), mean YPI 38.6 months.
Methodology: Comparison of pituitary and adrenal function with age and gender matched AB controls.
Outcome measure: Immunoassay methods.
  1. Plasma cortisol and dehydroepiandrosterone sulfate (DS) were higher in persons with SCI.
  2. When examined within level of injury, no differences on mean plasma cortisol emerged, but persons with tetraplegia had higher levels of mean plasma dehydroepiandrosterone sulfate than AB controls which may suggest adrenal dysfunction.

Campagnolo et al. 1994; USA
Cross-sectional with AB controls
N SCI=5
N controls=5

 Population: 5 participants with complete tetraplegia (4M 1F); mean age 36.2 yrs, (range 20-69 yrs); mean YPI 33.8 (range 7-120 mos).
Methodology: Comparison of an immunologic parameter, and psychological wellbeing with age and gender matched AB controls.
Outcome measure: Lymphocyte proliferation assay; Natural killer cell cytotoxicity assay; Cell counts; Ilfeld Psychiatric Symptom Index.
  1. No difference in cytometry, depression or stress.
  2. Participants with SCI had significant suppression in lymphocyte balstogenic response for the three mitogens tested (pokeweed, conconavalin, phytohemagglutinin).

Discussion

One study provides level 4 evidence (Frisbie 2010) that persons with SCI have a high prevalence of anemia and hypoalbuminemia which might serve as markers for infection. Additionally, two studies provide level 5 evidence that this system is compromised at the acute and chronic stages of SCI compared with AB controls. Persons with acute and chronic SCI who have complete injuries (N = 5) demonstrated altered immune function compared to AB controls (Campagnolo et al. 1994). As well, Campagnolo et al. (1999) compared persons with SCI (N = 18) to AB controls (N = 18), and found that persons with SCI have higher levels of cortisol and dehydroepiandrosterone sulfate (DS), but comparable levels of dehydroepiandrosterone, adrenocorticotropin, and prolactin. Additionally, they found that DS and dehydroepiandrosterone were higher in persons with tetraplegia compared to controls, but no differences were found between persons with paraplegia and controls. Campagnolo et al. (1999) concluded that immune functioning is altered after SCI, but may be mediated by level of injury. Thus, persons with tetraplegia may have a greater degree of alteration to the immune system compared to persons with paraplegia. Unfortunately, the sample sizes in both studies were quite small.

Further research related to the immune system is required given that older age of SCI-onset leads to poorer outcomes (Prusmack et al. 2006), and SCI of long duration results in increased infection (Whiteneck et al. 1992). Because persons with SCI are treated with antiobiotics throughout their lives, there are a number of important questions regarding the long-term effects on the immune system (Adkins 2004).

Conclusion

There is Level 4 evidence that persons with SCI have a prevalence of anemia and hypoalbuminemia (Frisbie 2010), which might serve as markers for infection.

There is Level 5 evidence (Campagnolo et al. 1994; Campagnolo et al. 1999; Furlan et al. 2006) that the immune function of persons with acute and chronic SCI is compromised compared to the able-bodied population, but there is no influence due to aging.

Immune function after SCI at both the acute and chronic phase is compromised compared to able-bodied controls, but age may not play an important role.

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