Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Profiling of T Cell Receptor β-Chain Complimentary Determining Regions 3 Repertoire in Subarachnoid Hemorrhage Patients Using High-Throughput Sequencing

  • Kim, Bong Jun (Institute of New Frontier Stroke Research, Hallym University College of Medicine) ;
  • Ahn, Jun Hyong (Department of Neurosurgery, Hallym University College of Medicine) ;
  • Youn, Dong Hyuk (Institute of New Frontier Stroke Research, Hallym University College of Medicine) ;
  • Jeon, Jin Pyeong (Institute of New Frontier Stroke Research, Hallym University College of Medicine)
  • Received : 2020.07.27
  • Accepted : 2020.10.07
  • Published : 2021.07.01
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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.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea funded by the Ministry of Education (2020R1l1A3070726), Hallym Research Fund, and Hallym University Research Fund (HURF-2019-29).

References

  1. Akamatsu Y, Pagan VA, Hanafy KA : The role of TLR4 and HO-1 in neuroinflammation after subarachnoid hemorrhage. J Neurosci Res 98 : 549-556, 2020 https://doi.org/10.1002/jnr.24515
  2. Attaf M, Huseby E, Sewell AK : αβ T cell receptors as predictors of health and disease. Cell Mol Immunol 12 : 391-399, 2015 https://doi.org/10.1038/cmi.2014.134
  3. Boyd SD, Joshi SA : High-throughput DNA sequencing analysis of antibody repertoires. Microbiol Spectr 2, 2014
  4. Carlson CS, Emerson RO, Sherwood AM, Desmarais C, Chung MW, Parsons JM, et al. : Using synthetic templates to design an unbiased multiplex PCR assay. Nat Commun 4 : 2680, 2013. https://doi.org/10.1038/ncomms3680
  5. Chang CM, Hsu YW, Wong HS, Wei JC, Liu X, Liao HT, et al. : Characterization of T-cell receptor repertoire in patients with rheumatoid arthritis receiving biologic therapies. Dis Markers 2019 : 2364943, 2019
  6. Chen J, Chen G, Li J, Qian C, Mo H, Gu C, et al. : Melatonin attenuates inflammatory response-induced brain edema in early brain injury following a subarachnoid hemorrhage: a possible role for the regulation of pro-inflammatory cytokines. J Pineal Res 57 : 340-347, 2014 https://doi.org/10.1111/jpi.12173
  7. Cho YD, Kim SE, Lim JW, Choi HJ, Cho YJ, Jeon JP : Protected versus unprotected carotid artery stenting : meta-analysis of the current literature. J Korean Neurosurg Soc 61 : 458-466, 2018 https://doi.org/10.3340/jkns.2017.0202.001
  8. Dupic T, Marcou Q, Walczak AM, Mora T : Genesis of the αβ T-cell receptor. PLoS Comput Biol 15 : e1006874, 2019 https://doi.org/10.1371/journal.pcbi.1006874
  9. Gomez-Tourino I, Kamra Y, Baptista R, Lorenc A, Peakman M : T cell receptor β-chains display abnormal shortening and repertoire sharing in type 1 diabetes. Nat Commun 8 : 1792, 2017 https://doi.org/10.1038/s41467-017-01925-2
  10. Hansson GK : Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352 : 1685-1695, 2005 https://doi.org/10.1056/NEJMra043430
  11. Hong EP, Kim BJ, Cho SS, Yang JS, Choi HJ, Kang SH, et al. : Genomic variations in susceptibility to intracranial aneurysm in the Korean population. J Clin Med 8 : 275, 2019. https://doi.org/10.3390/jcm8020275
  12. Hou X, Wang M, Lu C, Xie Q, Cui G, Chen J, et al. : Analysis of the repertoire features of TCR beta chain CDR3 in human by high-throughput sequencing. Cell Physiol Biochem 39 : 651-667, 2016 https://doi.org/10.1159/000445656
  13. Jeon JS, Ahn JH, Moon YJ, Cho WS, Son YJ, Kim SK, et al. : Expression of cellular retinoic acid-binding protein-I (CRABP-I) in the cerebrospinal fluid of adult onset moyamoya disease and its association with clinical presentation and postoperative haemodynamic change. J Neurol Neurosurg Psychiatry 85 : 726-731, 2014 https://doi.org/10.1136/jnnp-2013-305953
  14. Jia L, Zhu L, Wang JZ, Wang XJ, Chen JZ, Song L, et al. : Methylation of FOXP3 in regulatory T cells is related to the severity of coronary artery disease. Atherosclerosis 228 : 346-352, 2013 https://doi.org/10.1016/j.atherosclerosis.2013.01.027
  15. Kamel H, Iadecola C : Brain-immune interactions and ischemic stroke: clinical implications. Arch Neurol 69 : 576-581, 2012 https://doi.org/10.1001/archneurol.2011.3590
  16. Kim BJ, Kim Y, Hong EP, Jeon JP, Yang JS, Choi HJ, et al. : Correlation between altered DNA methylation of intergenic regions of ITPR3 and development of delayed cerebral ischemia in patients with subarachnoid hemorrhage. World Neurosurg 130 : e449-e456, 2019 https://doi.org/10.1016/j.wneu.2019.06.113
  17. Kim BJ, Kim Y, Youn DH, Park JJ, Rhim JK, Kim HC, et al. : Genome-wide blood DNA methylation analysis in patients with delayed cerebral ischemia after subarachnoid hemorrhage. Sci Rep 10 : 11419, 2020 https://doi.org/10.1038/s41598-020-68325-3
  18. Kim BJ, Youn DH, Kim Y, Jeon JP : Characterization of the TCR β Chain CDR3 repertoire in subarachnoid hemorrhage patients with delayed cerebral ischemia. Int J Mol Sci 21 : 3149, 2020 https://doi.org/10.3390/ijms21093149
  19. Kim CH, Jeon JP, Kim SE, Choi HJ, Cho YJ : Endovascular treatment with intravenous thrombolysis versus endovascular treatment alone for acute anterior circulation stroke : a meta-analysis of observational studies. J Korean Neurosurg Soc 61 : 467-473, 2018 https://doi.org/10.3340/jkns.2017.0505.006
  20. Kim HC, Rhim JK, Ahn JH, Park JJ, Moon JU, Hong EP, et al. : Machine learning application for rupture risk assessment in small-sized intracranial aneurysm. J Clin Med 8 : 683, 2019. https://doi.org/10.3390/jcm8050683
  21. Komotar RJ, Schmidt JM, Starke RM, Claassen J, Wartenberg KE, Lee K, et al. : Resuscitation and critical care of poor-grade subarachnoid hemorrhage. Neurosurgery 64 : 397-410, 2009 https://doi.org/10.1227/01.NEU.0000338946.42939.C7
  22. Li D, Hu L, Liang Q, Zhang C, Shi Y, Wang B, et al. : Peripheral T cell receptor beta immune repertoire is promptly reconstituted after acute myocardial infarction. J Transl Med 17 : 40, 2019 https://doi.org/10.1186/s12967-019-1788-4
  23. Marik PE, Flemmer M : The immune response to surgery and trauma: implications for treatment. J Trauma Acute Care Surg 73 : 801-808, 2012 https://doi.org/10.1097/TA.0b013e318265cf87
  24. Mathiesen T, Andersson B, Loftenius A, von Holst H : Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage. J Neurosurg 78 : 562-567, 1993 https://doi.org/10.3171/jns.1993.78.4.0562
  25. Moraes L, Grille S, Morelli P, Mila R, Trias N, Brugnini A, et al. : Immune cells subpopulations in cerebrospinal fluid and peripheral blood of patients with aneurysmal subarachnoid hemorrhage. Springerplus 4 : 195, 2015 https://doi.org/10.1186/s40064-015-0970-2
  26. Okazaki T, Kuroda Y : Aneurysmal subarachnoid hemorrhage: intensive care for improving neurological outcome. J Intensive Care 6 : 28, 2018 https://doi.org/10.1186/s40560-018-0297-5
  27. Park JJ, Kim BJ, Youn DH, Choi HJ, Jeon JP : A Preliminary Study of the Association between SOX17 gene variants and intracranial aneurysms using exome sequencing. J Korean Neurosurg Soc 63 : 559-565, 2020 https://doi.org/10.3340/jkns.2019.0225
  28. Robins H, Desmarais C, Matthis J, Livingston R, Andriesen J, Reijonen H, et al. : Ultra-sensitive detection of rare T cell clones. J Immunol Methods 375 : 14-19, 2012 https://doi.org/10.1016/j.jim.2011.09.001
  29. Robins HS, Campregher PV, Srivastava SK, Wacher A, Turtle CJ, Kahsai O, et al. : Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood 114 : 4099-4107, 2009
  30. Sims JS, Grinshpun B, Feng Y, Ung TH, Neira JA, Samanamud JL, et al. : Diversity and divergence of the glioma-infiltrating T-cell receptor repertoire. Proc Natl Acad Sci U S A 113 : E3529-E3537, 2016 https://doi.org/10.1073/pnas.1601012113
  31. Sun J, Sun B, Gao Y, He F, Yang L, Wang M, et al. : Composition and variation analysis of the T cell receptor β-chain complementarity determining region 3 repertoire in neonatal sepsis. Scand J Immunol 86 : 418-423, 2017 https://doi.org/10.1111/sji.12614
  32. Yang G, Ou M, Chen H, Guo C, Chen J, Lin H, et al. : Characteristic analysis of TCR β-chain CDR3 repertoire for pre- and post-liver transplantation. Oncotarget 9 : 34506-34519, 2018 https://doi.org/10.18632/oncotarget.26138
  33. Youn DH, Kim BJ, Kim Y, Jeon JP : Extracellular mitochondrial dysfunction in cerebrospinal fluid of patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neurocrit Care 33 : 422-428, 2020 https://doi.org/10.1007/s12028-019-00895-1
  34. Yu J, Shi B, Ma L, Liu C, Sun S, Ma R, et al. : Case report for recurrent and new-onset SLE patients treated by high-dose glucocorticoid therapy: characteristics of peripheral TCR beta chain CDR3 repertoires. Medicine (Baltimore) 96 : e9022, 2017 https://doi.org/10.1097/MD.0000000000009022