Expression of alpha 1 subunit in the Haptoglobin 2‐1 phenotype and its association with clinical course in aneurysmal subarachnoid hemorrhage

Abstract

ObjectDelayed cerebral ischemia (DCI) due to vasospasm contribute to poor clinical outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). Free hemoglobin (Hb) following hemolysis within the subarachnoid space has been thought to trigger vasospasm through oxidative radical and local inflammatory reactions. Haptoglobin (Hp), tetrameric protein comprised of two light chains (α) and two heavy chains (β), provides anti‐oxidant neutralization by binding to free Hb and its subsequent clearance by macrophages. In human, differences of α chain results in three phenotypes: Hp1‐1 (two α1 chains), Hp2‐1 (α1 and α2 chains), and Hp2‐2 (two α2 chains). Although protective effect against for toxic free Hb has been reported in SAH patients with Hp 2‐2 than those with Hp 1‐1, significance of Hp 2‐1 focusing on the expression of α1 subunit has not been well investigated. The aims of this study was to determine the association between intensity of α1 subunit and clinical courses in SAH patients.MethodsThis study examined the plasma from 86 patients: Hp 1‐1, n=12 (14.0%); Hp 2‐1, n=35 (40.7%), and Hp 2‐2, n=39 (45.3%). α1 intensity was confirmed by western blotting and expressed as the median (25th–75th percentile) in patients with Hp 2‐1. The relative intensity was measured as the intensity of α1 divided by the intensity of albumin. The difference in α1 intensity according to DCI, angiographic vasospasm and good outcome (mRS 0–2) on 3 months were analyzed.ResultsFor three Hp phenotypes, DCI and angiographic vasospasm were more frequently observed in Hp 2‐2 (DCI, n=21 (53.8%) and angiographic vasospasm, n=24 (61.5%)) and Hp 2‐1 (DCI, n=12 (34.3%) and angiographic vasospasm, n=18 (51.4%)) and compared to Hp 1‐1 (DCI, n=3 (25.0%); and angiographic vasospasm, n=4 (33.3%)). Other variables such as clinical (sex, age, hypertension, diabetes mellitus, dyslipidemia, and smoking), treatment types (endovascular coiling and surgical clipping), and initial patients' condition (Hunt‐Hess grade and Fisher grade) did not reach any significance according to three Hp phenotypes. Regarding Hp 2‐1, significant higher levels of α1 intensities were noted in SAH patient without DCI (0.79 (0.42–0.92)) and angiographic vasospasm (0.86 (0.75–0.99)) compared to those with DCI (0.18 (0.15–0.23), p<0.001) and angiographic vasospasm (0.22 (0.18–0.41), p<0.001). Patients with good neurologic outcome (0.75 (0.38–0.91)) tended to exhibit elevated α1 intensities, but not statistically significant (0.20 (0.18–0.65), p=0.107).ConclusionsHp 2‐1 and Hp 2‐2 seem to have higher incidence of DCI and vasospasm than Hp 1‐1 in patients presenting with aneurysmal SAH. Higher α1 intensities in Hp 2‐1 type can be associated with lower incidence of DCI and angiographic vasospasm. The intensity degree may provide additional information on individual risk of secondary injury following SAH.Support or Funding InformationThis work was supported by National Research Foundation of Korea (NFR) grant funded by the Korea government (NRF‐2017M3A9E8033223, NRF‐2017R1C1B5016678)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.