Longitudinal immune profiling demonstrates persistent MAIT cell reduction and temporal cytokine alterations after aneurysmal subarachnoid hemorrhage.

Background: Neuroinflammation and systemic immune dysregulation are increasingly recognized as key contributors to secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). However, the temporal relationship between circulating cytokine responses and innate-like lymphocyte populations, particularly mucosal-associated invariant T (MAIT) cells, remains poorly characterized. Methods: In this prospective observational study, peripheral blood cytokine profiles were longitudinally analyzed in 48 patients with aSAH on days 1, 5, and 9 after ictus and compared with healthy controls. Serum concentrations of IL-6, IL-7, IL-12p40, IL-12p70, IL-15, IL-17A, IL-18, IL-22, IP-10, and CXCL-9 were measured using multiplex immunoassay. Flow cytometric immunophenotyping was performed in a subgroup of 16 patients to evaluate MAIT cells, NK cells, γδ T cells, iNKT cells, and NKT-like cells. Associations between immune parameters and 3-month functional outcome were also assessed. Results: Patients with aSAH demonstrated persistently elevated IL-6, IL-18, and IL-15 levels across all examined time points, while IL-7, IL-12p40, IP-10, and CXCL-9 showed delayed increases during the subacute phase. IL-6 and IL-15 concentrations were significantly higher in patients with unfavorable outcome, whereas IL-22 levels were increased in patients with favorable recovery. However, these associations were not independent of disease severity after adjustment for WFNS score and age. Flow cytometry revealed a persistent reduction in circulating MAIT-cell frequencies following aSAH, while other innate-like lymphocyte populations remained largely unchanged. DN MAIT-cell frequencies demonstrated significant negative correlations with circulating IL-18 levels across all examined time points. Conclusion: aSAH is associated with sustained systemic inflammatory activation and selective alterations of MAIT-cell populations. Although several cytokines were associated with functional outcome in univariate analyses, these associations were attenuated after adjustment for WFNS score and age, suggesting that they primarily reflect disease severity rather than independent prognostic effects. The observed relationship between MAIT-cell dysregulation and IL-18-associated inflammation provides further evidence of altered innate-like immune responses following aSAH.