Subarachnoid hemorrhage induces expansion of pro-inflammatory lymphocyte subsets in human cerebrospinal fluid: a pilot study.

Despite recent advances in treatment, subarachnoid hemorrhage from a ruptured brain aneurysm (aSAH) remains a significant cause of morbidity and mortality worldwide. While some early effects of aneurysm rupture (direct trauma to brain tissue, for example) are unrelated to the immune response, research suggests that some early and many delayed effects of aSAH such as vasospasm, delayed cerebral ischemia, chronic neurological decline, are at least partially immune mediated. Cytokines, neutrophils, and other immune markers are known to correlate with these delayed sequelae. Based on our prior work, we hypothesized that aSAH may initiate an immune response characterized by expansion of pro-inflammatory B cells that stain positive for the cleavage product of major histocompatibility complex (MHC) Class II invariant chain (CLIP). We also hypothesized that other lymphocyte populations may increase surface expression of HLA-DR, the surface component of MHC Class II. To investigate this concept, we collected peripheral blood and cerebrospinal fluid from aSAH patients on days 1, 7, and 14 following aneurysm rupture. Live leukocytes were isolated and stained with fluorochrome-linked antibodies against: CD3, CD4, CD8, CD19, CLIP, HLA-DR, and CD56 and analyzed by flow cytometry. In CSF, both CLIP+ CD19+ (B cells) and CLIP+ CD56+ (NK cells) populations significantly increased over several days following aSAH. Furthermore, HLA-DR+ CD4+ T cells, HLA-DR+ CD8+ T cells, and HLA-DR+ CD56+ NK cells showed a significant increase in the CSF as well. These data suggest that, following aSAH, several pro-inflammatory lymphocyte subtypes significantly increase in CSF as part of an immune response.