J Korean Neurosurg Soc.  2021 Jul;64(4):505-513. 10.3340/jkns.2020.0214.

Profiling of T Cell Receptor β-Chain Complimentary Determining Regions 3 Repertoire in Subarachnoid Hemorrhage Patients Using High-Throughput Sequencing

Affiliations
  • 1Institute of New Frontier Stroke Research, Hallym University College of Medicine, Chuncheon, Korea
  • 2Department of Neurosurgery, Hallym University College of Medicine, Chuncheon, Korea
  • 3Genetic and Research Inc., Chuncheon, Korea

Abstract


Objective
: The adaptive immune response following subarachnoid hemorrhage (SAH) is not well understood. We evaluated and compared the T cell receptor (TCR) immune repertoire of good-grade and poor-grade SAH patients to elucidate the T cell immunology after ictus.
Methods
: Peripheral blood from six SAH patients was collected at two different times, admission and at the 7-day follow-up. Composition and variation of the TCR β-chain (TCRB) complimentary determining regions (CDR) 3 repertoire was examined using high-throughput sequencing; the analysis was based on sampling time and disease severity (good vs. poor-grade SAH).
Results
: Clonality at admission and follow-up were 0.059 (0.037–0.038) and 0.027 (0.014–0.082) (median, 25th–75th percentile). Poor-grade SAH (0.025 [0.011–0.038]) was associated with significantly lower clonality than good-grade SAH (0.095 [0.079–0.101]). Poor-grade SAH patients had higher diversity scores than good-grade SAH patients. CDR length was shorter in good-grade SAH vs. poor-grade SAH. Differences in clonotype distribution were more prominent in TCRBV gene segments than TCRBJ segments. TCRBV19-01/TCRBJ02-04 and TCRBV28-01/TCRBJ02-04 were the most increased and the most decreased V-J pairs in the 7-day follow-up compared to admission in good-grade SAH. The most increased and decreased V-J pairs in poor-grade SAH patients were TCRBV28-01/TCRBJ02-06 and TCRBV30-01/TCRBJ02-04, respectively.
Conclusion
: The TCRB repertoire is dynamic in nature following SAH. TCRB repertoire may facilitate our understanding of adaptive immune response according to SAH severity.

Keyword

Subarachnoid hemorrhage; T cell receptor beta; Immunity; High-throughput sequencing

Figure

  • Fig. 1. Comparison of TCRB clonality (A) and CDR3 length repertoire (B) according to SAH severity, good- vs. poor-grade. Good-grade SAH patients had higher clonality and shorter CDR3 length than did poor-grade SAH patients. CDR : complimentary determining regions, TCRB : T cell receptor β-chain, SAH : subarachnoid hemorrhage.

  • Fig. 2. Quantification of TCRB CDR3 sequences in each patient between the day of admission and the 7-day follow-up. The 10 most common sequences are presented in different colors. Patients who presented with poor-grade SAH tended to show a low proportion of the top 10 most common sequences compared to those with good-grade SAH at admission. Adm : admission, F/U : follow-up, TCRB : T cell receptor β-chain, CDR : complimentary determining regions, SAH : subarachnoid hemorrhage.

  • Fig. 3. Distribution and change in the unique clonotypes of the TCRBV and TCRBJ genes in patients with SAH. Compared to TCRBJ, TCRBV showed different distributions between the day of admission and the 7-day follow-up. Different colors are used to represent gene frequencies in each patient. TCRBJ : T cell receptor β chain J segment, TCRBV : T cell receptor β chain V segment, Adm : admission, F/U : follow-up, SAH : subarachnoid hemorrhage.

  • Fig. 4. Comparison of average TCRB V-J gene utilization at admission and during the 7-day follow-up according to SAH severity of good (A) and poor (B)-grade. V gene and J gene segments are arranged on the x- and y-axis. Different colors indicate the differences in gene frequencies of poor-grade SAH patients compared with good-grade SAH patients. TCRB : T cell receptor β-chain, SAH : subarachnoid hemorrhage.


Reference

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