Deep Immunophenotyping deckt Depletion von entzündungshemmenden T-Helfer-Typ-2-Zellen (Th2) auf und verbindet den Verlust von alternativ aktivierten Monozyten (M2) mit Vasospasmus und Delayed Cerebral Ischemia nach aneurysmatischer Subarachnoidalblutung

A sterile inflammatory response initiated immediately after aneurysmal subarachnoid haemorrhage (aSAH) heavily contributes to post-aSAH complications and clinical outcomes. Circulating immune cells, particularly monocytes and T cells, depending on their polarisation form and activation status, hereby play a decisive role. The exact dynamic of subgroup polarisation and their role after aSAH is unclear. Therefore, this prospective and controlled study investigated monocyte and T-cell polarisation after aSAH to explore dynamic changes over the course of aSAH and their association with post-SAH complications and clinical outcomes.

We conducted a prospective observational cohort study involving 75 patients with aSAH. Twenty healthy controls were enrolled for this study. Deep immunophenotyping of T-cells and Monocytes was performed using multi-colour FACS analysis on days 1, 4, 7, and 11 post-aSAH. Clinical events, including macro vasospasm, cerebral infarction, and the outcome (mRS 6 months 0-2 vs 3-5 vs 6) were recorded prospectively and analysed using ANOVA and following post-hoc t-tests.

Patients with aSAH displayed reduced alternatively activated monocytes (M2) (3.0% vs 6.3% of all monocytes; p=0.04) and Th2 T cells (45.5% vs 75.3% of all T cells; p<0.001) within 24h after bleeding compared to healthy individuals. Prior to macro vasospasm, patients depict relative reduction in alternatively activated monocytes (M2) (2.0% vs 4.0% of all monocytes; p=0.019) and relative increase in proinflammatory Th1 T cells (15.8% vs 9.3% of all t cells; p=0.0022). Likewise, prior to cerebral infarction, patients showed a relative reduction in anti-inflammatory alternatively activated monocytes (M2) (2.7% vs 4.1% of all monocytes; p=0.049). No significant correlation was observed with patient outcomes (for all p>0.61).

Aneurysmal SAH led to an enhanced pro-inflammatory response, inducing an early shift of monocyte and T-cells towards classical inflammatory phenotypes. Patients confronting CVS or DCI revealed a loss of alternatively activated monocytes (M2) and Th2 T cells shortly after the bleeding prior to macro vasospasm and cerebral infarction. Reconstitution of anti-inflammatory monocytes and T-cells can be exploited to combat vasospasm and confer neuroprotection after aSAH.