Characterization of the TCR β Chain CDR3 Repertoire in Subarachnoid Hemorrhage Patients with Delayed Cerebral Ischemia

Int J Mol Sci. 2020 Apr 29;21(9):3149. doi: 10.3390/ijms21093149.

Abstract

Little is known of the adaptive immune response to subarachnoid hemorrhage (SAH). This study was the first to investigate whether T cell receptor (TCR) immune repertoire may provide a better understanding of T cell immunology in delayed cerebral ischemia (DCI). We serially collected peripheral blood in five SAH patients with DCI. High-throughput sequencing was used to analyze the TCR β chain (TCRB) complimentary determining regions (CDR) 3 repertoire. We evaluated the compositions and variations of the repertoire between admission and the DCI period, for severe DCI and non-severe DCI patients. Clonality did not differ significantly between admission and DCI. Severe DCI patients had significantly lower clonality than non-severe DCI patients (p value = 0.019). A read frequency of 0.005% ≤ - < 0.05% dominated the clonal expansion in non-severe DCI patients. Regarding repertoire diversity, severe DCI had a higher diversity score on admission than non-severe DCI. The CDR3 lengths were similar between admission and DCI. Among 728 annotated V-J gene pairs, we found that the relative frequencies of two V-J pairs were different at the occurrence of DCI than at admission, with T cells increasing by over 15%. TCRB CDR3 repertoires may serve as biomarkers to identify severe DCI patients.

Keywords: T cell receptor β; delayed cerebral ischemia; subarachnoid hemorrhage.

MeSH terms

  • Brain Ischemia / etiology*
  • Clonal Evolution / genetics
  • Clonal Evolution / immunology
  • Complementarity Determining Regions / genetics*
  • Complementarity Determining Regions / metabolism
  • Computational Biology / methods
  • Disease Susceptibility
  • Female
  • Gene Expression Profiling
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Humans
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / etiology*
  • Subarachnoid Hemorrhage / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell, alpha-beta