Variation of membrane particle-bound CD133 in cerebrospinal fluid of patients with subarachnoid and intracerebral hemorrhage

Objective: Previous studies have demonstrated that human CSF contains membrane particles carrying the stem cell antigenic marker CD133 (prominin-1). Here, the authors analyzed the variation of the amount of these CD133-positive particles in the CSF of patients with subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH).

Methods: Consecutive CSF samples from 47 patients with SAH or ICH were compared to 14 healthy control patients. After differential ultracentrifugation of CSF, the membrane particle fraction was separated on gel electrophoresis and its CD133 content was probed by immunoblotting using the mouse monoclonal antibody 80B258 directed against human CD133. The antigen-antibody complexes were detected by chemiluminescence reagents and quantified using human Caco-2 cell extract as positive control with a standardized curve.

Results: As compared to healthy controls (6.3 ± 0.5 ng of bound CD133 antibody; n = 14), the amount of membrane particle-associated CD133 immunoreactivities was significantly elevated in patients with SAH and ICH (38.2 ± 6.6 ng and 61.3 ± 11.0 ng [p < 0.001] for SAH [n = 18] and ICH [n = 29], respectively). In both groups the CD133 level dropped during the first 7 days (i.e., day 5-7: SAH group, 24.6 ± 10.1 ng [p = 0.06]; ICH group, 25.0 ± 4.8 ng [p = 0.002]). Whereas changes in the amount of CD133-positive membrane particles between admission and day 5-7 were not associated with clinical outcomes in patients with ICH (modified Rankin Scale [mRS] scores 0-3, -30.9 ± 12.8 ng vs mRS scores 4-6, -21.8 ± 10.7 ng; p = 0.239), persistent elevation of CD133 in patients with SAH was related to impaired functional outcome 3 months after ictus (mRS scores 0-2, -29.9 ± 8.1 ng vs mRS scores 3-6, 7.6 ± 20.3 ng; p = 0.027). These data are expressed as the mean ± standard error of the mean (SEM).

Conclusions: Levels of membrane particle-associated CD133 in the CSF of patients with SAH and ICH are significantly increased in comparison to healthy patients, and they decline during the hospital stay. Specifically, the persistent elevation of CD133-positive membrane particles within the first week may represent a possible surrogate measure for impaired functional outcome in patients with SAH.