Evidence map›Paper›PMID 30455696›Full record

ArticleFrontiers in immunology2018

Clinical T Cell Receptor Repertoire Deep Sequencing and Analysis: An Application to Monitor Immune Reconstitution Following Cord Blood Transplantation.

Athina Soragia Gkazi, Ben K Margetts, Teresa Attenborough, Lana Mhaldien, Joseph F Standing, Theres Oakes, James M Heather, John Booth, Marlene Pasquet, Robert Chiesa and 5 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed.

  1. Trial
  2. Analysis of the Whole CDR3 T Cell Receptor Repertoire after Hematopoietic Stem Cell Transplantation in 2 Clinical Cohorts.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Athina Soragia GkaziInfection, Immunity and Inflammation Section, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Ben K MargettsInfection, Immunity and Inflammation Section, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Teresa AttenboroughInfection, Immunity and Inflammation Section, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Lana MhaldienSIHMDS-Haematology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
Joseph F StandingInfection, Immunity and Inflammation Section, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Theres OakesDivision of Infection and Immunity, University College London, London, United Kingdom.
James M HeatherDivision of Infection and Immunity, University College London, London, United Kingdom.
John BoothDigital Research Environment, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
Marlene PasquetLe Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Robert ChiesaDepartment of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
Paul VeysDepartment of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
Nigel KleinInfection, Immunity and Inflammation Section, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Benny ChainDivision of Infection and Immunity, University College London, London, United Kingdom.
Robin CallardInfection, Immunity and Inflammation Section, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Stuart P AdamsInfection, Immunity and Inflammation Section, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.

Funding

Cancer Research UK 20265
6 · The paper itself

Abstract

Spectratyping assays are well recognized as the clinical gold standard for assessing the T cell receptor (TCR) repertoire in haematopoietic stem cell transplant (HSCT) recipients. These assays use length distributions of the hyper variable complementarity-determining region 3 (CDR3) to characterize a patient's T cell immune reconstitution post-transplant. However, whilst useful, TCR spectratyping is notably limited by its resolution, with the technique unable to provide data on the individual clonotypes present in a sample. High-resolution clonotype data are necessary to provide quantitative clinical TCR assessments and to better understand clonotype dynamics during clinically relevant events such as viral infections or GvHD. In this study we developed and applied a CDR3 Next Generation Sequencing (NGS) methodology to assess the TCR repertoire in cord blood transplant (CBT) recipients. Using this, we obtained comprehensive TCR data from 16 CBT patients and 5 control cord samples at Great Ormond Street Hospital (GOSH). These were analyzed to provide a quantitative measurement of the TCR repertoire and its constituents in patients post-CBT. We were able to both recreate and quantify inferences typically drawn from spectratyping data. Additionally, we demonstrate that an NGS approach to TCR assessment can provide novel insights into the recovery of the immune system in these patients. We show that NGS can be used to accurately quantify TCR repertoire diversity and to provide valuable inference on clonotypes detected in a sample. We serially assessed the progress of T cell immune reconstitution demonstrating that there is dramatic variation in TCR diversity immediately following transplantation and that the dynamics of T cell immune reconstitution is perturbed by the presence of GvHD. These findings provide a proof of concept for the adoption of NGS TCR sequencing in clinical practice.

Indexed as

Cord Blood Stem Cell TransplantationHematopoietic Stem Cell TransplantationBase SequenceChildChild, PreschoolComplementarity Determining RegionsGraft vs Host DiseaseHigh-Throughput Nucleotide SequencingHumansImmune ReconstitutionInfantInfant, NewbornReceptors, Antigen, T-CellSequence Analysis, DNAT-LymphocytesComplementarity Determining RegionsReceptors, Antigen, T-CellCDR3clonotypeshaematopoietic stem cell transplantimmune reconstitutionnext generation sequencingT cellT cell receptor

Identifiers

PMID30455696
PMCPMC6231291

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.