Immunodepression in aneurysmal subarachnoid hemorrhage patients
Immunology
Final Report Abstract
In 75 aneurysmal subarachnoid hemorrhage (aSAH) patients, a detailed immune monitoring was performed to determine the association between disease severity, immunological changes and clinical outcome. To analyse changes in leukocyte subsets, marker of immunodepression (mHLA-DR, LPS-induced TNFa, ConA-induced IFNg, plasma IL-10), inflammation (IL-6) and infection (LBP) over time after hemorrhage, blood samples were collected on days 1, 3, 6, 9, 12 and 15 after hemorrhage at 8:00 AM. A follow-up sample was taken at 6 months after aSAH from surviving patients (n=52). Patients were predominantly female; mean age was 54.4 ± 11.8 years. Majority of patients (n=42, 56%) presented with high grade SAH according to the WFNS-grading. Aneurysm localization was mainly in the anterior circulation (70%), most frequently Acom-and MCA- aneurysms. 10 of 33 patients (33.3%) with low WFNS grade developed delayed cerebral ischemia (DCI) while 26 of 42 patients with high grade WFNS patients developed a DCI (61.9%, p= 0.010). A non-favorable WFNS grade increased the risk for DCI by 2.04 (relative risk, 95% CI = 1.16-3,.61). Overall, in 41 of 75 patients the occurrence of any type of infection was documented. Hospital acquired pneumonia (HAP) was the most frequent type of infection detected in 24 patients (59%). The incidence of HAP was about half as much in patients with low grade WFNS (7 of 33, 21.2%) compared to high grade WFNS (17 of 42, 40.5%), but not significant (p = 0.087). However, a significantly higher proportion of patients with DCI (18 of 36, 50.0%) developed HAP compared to patients without DCI (6 of 39, 15.4%; p=0.003). The change over time was locally significant (not adjusted for multiplicity) for 12 of 13 examined immune markers. Locally significant differences were found for 9 out of 15 markers. Most differences remained significant with Bonferroni correction. We observed significant decreases for NK cells (p<0.001), B cells (p=0.049), CD8+ T cells (p = 0.002), mHLA-DR (p= .003), and ConA-induced IFNg (p<0.0005). Significant increases were observed for Granulocytes (p<0.0001), IL6 (p<0.0001), and Leukocytes (p<0.0001). Significantly higher levels of IL-6 were found in the presence of infection (p=0.009), in patients with high WFNS score (p=0.009) or development of DCI (p=0.008) and in non-survivors (p=0.0005). Low mHLA-DR levels were significantly associated with the development of infections (p=0.029) and DCI (p=0.012). In addition, patients with infections showed significantly reduced values for NK cells, B cells, LPS-induced TNFa, and mHLA-DR. In contrast, they showed significantly increased values for IL-6 and LBP. Patients with high WFNS showed locally significantly reduced values for CD4 T cells and ConA-induced IFNg, but increased values for IL-6. Patients with DCI showed locally significantly reduced values for NK cells, CD4+ T cells, and mHLA-DR but increased values for IL-6. Non-survivors showed locally significantly reduced values for mHLADR but increased values for IL-6. In summary, mHLADR was consistently reduced for most investigated clinical outcomes while IL-6 was found increased. In conclusion, our data confirm our previous findings of the presence of profound immunodepression after aSAH in a larger patient cohort, and further demonstrate that immunodepression and infectious complications is more pronounced in patients with delayed cerebral ischemia.
