Resolving Immune Infiltrates in Brainstem Cerebral Cavernous Malformations Through Transcriptomic Signature Deconvolution. (16th November 2020) - Batchu, Sai
Abstract: INTRODUCTION: Accumulating evidence suggests involvement of immune cells in cerebral cavernous malformations (CCMs). However, the immunological landscape of CCMs located in the brainstem has yet to be examined. METHODS: The CIBERSORTx machine-learning algorithm was used to deconvolute bulk gene expression data developed from 10 brainstem CCMs and 4 control temporal lobe epilepsy (TLE) lesions. The algorithm accurately quantifies the relative fractions of distinct cell types within a complex expression mixture given cell type-specific gene signatures. The gene signatures used here were acquired from a validated microarray-derived matrix for distinguishing 22 human hematopoietic cell subsets. The non-parametric Mann Whitney U test was used for comparisons through R programming language. RESULTS: Compared to TLE lesions, brainstem CCMs showed significantly increased relative abundances of activated CD4 + memory T cells, M0 macrophages, and plasma cells ( P < .05). Within the CCM cohort, comparing lesions with no recent hemorrhage (NRH) (n = 7) to those recently hemorrhaged (RH) (n = 3) showed increased CD8 + T cells in NRH (p < 0.05). CONCLUSION: Brainstem CCMs exhibit an increased accumulation of certain immune cell types. Recent hemorrhage status is associated with differential cytotoxic T cell abundances within these lesions.