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RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance.
McCaffrey, Timothy A; Toma, Ian; Yang, Zhaoquing; Katz, Richard; Reiner, Jonathan; Mazhari, Ramesh; Shah, Palak; Tackett, Michael; Jones, Dan; Jepson, Tisha; Falk, Zachary; Wargodsky, Richard; Shtakalo, Dmitry; Antonets, Denis; Ertle, Justin; Kim, Ju H; Lai, Yinglei; Arslan, Zeynep; Aledort, Emily; Alfaraidy, Maha; Laurent, Georges St.
  • McCaffrey TA; Division of Genomic Medicine, Department of Medicine, The George Washington Medical Center, The George Washington University, 2300 I Street NW, Ross Hall 443A, Washington, DC, 20037, USA. mcc@gwu.edu.
  • Toma I; The St. Laurent Institute, Vancouver, WA, USA. mcc@gwu.edu.
  • Yang Z; Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC, 20037, USA. mcc@gwu.edu.
  • Katz R; True Bearing Diagnostics, Washington, DC, 20037, USA. mcc@gwu.edu.
  • Reiner J; Division of Genomic Medicine, Department of Medicine, The George Washington Medical Center, The George Washington University, 2300 I Street NW, Ross Hall 443A, Washington, DC, 20037, USA.
  • Mazhari R; Department of Clinical Research and Leadership, The George Washington University, Washington, DC, 20037, USA.
  • Shah P; True Bearing Diagnostics, Washington, DC, 20037, USA.
  • Tackett M; Division of Genomic Medicine, Department of Medicine, The George Washington Medical Center, The George Washington University, 2300 I Street NW, Ross Hall 443A, Washington, DC, 20037, USA.
  • Jones D; Division of Cardiology, Department of Medicine, The George Washington University , Washington, DC, 20037, USA.
  • Jepson T; Division of Cardiology, Department of Medicine, The George Washington University , Washington, DC, 20037, USA.
  • Falk Z; Division of Cardiology, Department of Medicine, The George Washington University , Washington, DC, 20037, USA.
  • Wargodsky R; Inova Heart and Vascular Institute, Fairfax, VA, USA.
  • Shtakalo D; SeqLL, Inc., Woburn, MA, USA.
  • Antonets D; SeqLL, Inc., Woburn, MA, USA.
  • Ertle J; SeqLL, Inc., Woburn, MA, USA.
  • Kim JH; The St. Laurent Institute, Vancouver, WA, USA.
  • Lai Y; True Bearing Diagnostics, Washington, DC, 20037, USA.
  • Arslan Z; Division of Genomic Medicine, Department of Medicine, The George Washington Medical Center, The George Washington University, 2300 I Street NW, Ross Hall 443A, Washington, DC, 20037, USA.
  • Aledort E; Division of Genomic Medicine, Department of Medicine, The George Washington Medical Center, The George Washington University, 2300 I Street NW, Ross Hall 443A, Washington, DC, 20037, USA.
  • Alfaraidy M; A.P. Ershov Institute of Informatics Systems SB RAS, 6, Acad. Lavrentjeva Ave, Novosibirsk, Russia, 630090.
  • Laurent GS; A.P. Ershov Institute of Informatics Systems SB RAS, 6, Acad. Lavrentjeva Ave, Novosibirsk, Russia, 630090.
BMC Med Genomics ; 14(1): 216, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1398860
ABSTRACT

BACKGROUND:

Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography. Surprisingly, despite well-established clinical indications, up to 40% of the one million invasive cardiac catheterizations return a result of 'no blockage'. The present studies employed RNA sequencing of whole blood to identify an RNA signature in patients with angiographically confirmed CAD.

METHODS:

Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by single-molecule sequencing of RNA (RNAseq) to identify transcripts associated with CAD (TRACs) in a discovery group of 96 patients presenting for elective coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs).

RESULTS:

Surprisingly, 98% of DEGs/TRACs were down-regulated ~ 1.7-fold in patients with mild to severe CAD (> 20% stenosis). The TRACs were independent of comorbid risk factors for CAD, such as sex, hypertension, and smoking. Bioinformatic analysis identified an enrichment in transcripts such as FoxP1, ICOSLG, IKZF4/Eos, SMYD3, TRIM28, and TCF3/E2A that are likely markers of regulatory T cells (Treg), consistent with known reductions in Tregs in CAD. A validation cohort of 80 patients confirmed the overall pattern (92% down-regulation) and supported many of the Treg-related changes. TRACs were enriched for transcripts associated with stress granules, which sequester RNAs, and ciliary and synaptic transcripts, possibly consistent with changes in the immune synapse of developing T cells.

CONCLUSIONS:

These studies identify a novel mRNA signature of a Treg-like defect in CAD patients and provides a blueprint for a diagnostic test for CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes, Regulatory Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Language: English Journal: BMC Med Genomics Journal subject: Genetics, Medical Year: 2021 Document Type: Article Affiliation country: S12920-021-01062-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes, Regulatory Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Language: English Journal: BMC Med Genomics Journal subject: Genetics, Medical Year: 2021 Document Type: Article Affiliation country: S12920-021-01062-2