Evidence map›Paper›PMID 36749920›Full record

ArticleBlood2023

The role of CD8+ T-cell clones in immune thrombocytopenia.

Amna Malik, Anwar A Sayed, Panpan Han, Michelle M H Tan, Eleanor Watt, Adela Constantinescu-Bercu, Alexander T H Cocker, Ahmad Khoder, Rocel C Saputil, Emma Thorley and 13 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06093529 (Marker Expression in Pediatric Patients With Immune Thrombocytopenic Purpura Receiving Second Line Therapy), which is not on this map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
14.8field-weighted citation impact, top 1% of its field
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.

NCT06093529 unknown statusnot on this mapstarted 2024, after this paper: background citation

Marker Expression in Pediatric Patients With Immune Thrombocytopenic Purpura Receiving Second Line Therapy

TypeobservationalSponsorAssiut UniversityRan2024 to 2025Enrolled42ConditionsITP - Immune ThrombocytopeniaArmscomplete blood count, CD3+ , CD4+ , CD8+, CD16+, CD56+, IFN-γ.
3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Clinical characteristics and decreased CD4Frontiers in immunology · 2026
    Article
  16. Article
  17. Article
  18. Review
  19. Correlation between the CD8Frontiers in pediatrics · 2026
    Article
  20. Refractory ITP: revisiting definitions, diagnostics, and management paradigms.Hematology. American Society of Hematology. Education Program · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 10 institutions in 4 countries.

Amna MalikCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.
Anwar A SayedCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.
Panpan HanDepartment of Pathology, Stanford University School of Medicine, Stanford, CA.
Michelle M H TanCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.
Eleanor WattSpecialist Integrated Haematology and Malignancy Diagnostic Service-Haematology, Great Ormond Street Hospital for Children, London, United Kingdom.ORCID 0000-0002-9571-0819
Adela Constantinescu-BercuCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.
Alexander T H CockerCentre for Immunology and Vaccinology, Imperial College London, London, United Kingdom.ORCID 0000-0001-7162-0774
Ahmad KhoderCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.
Rocel C SaputilCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.
Emma ThorleyCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.ORCID 0000-0001-7153-2547
Ariam TeklemichaelCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.ORCID 0000-0003-3873-1602
Yunchuan DingCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.
Alice C J HartCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.
Haiyu ZhangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA.
Wayne A MitchellDepartment of Immunology and Inflammation, Imperial College London, London, United Kingdom.
Nesrina ImamiCentre for Immunology and Vaccinology, Imperial College London, London, United Kingdom.ORCID 0000-0001-9673-2895
James T B CrawleyCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.ORCID 0000-0002-6723-7841
Isabelle I Salles-CrawleyCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.ORCID 0000-0001-7394-0587
James B BusselDepartment of Pediatrics, Weill Cornell Medicine, New York, NY.
James L ZehnderDepartment of Pathology, Stanford University School of Medicine, Stanford, CA.
Stuart AdamsSpecialist Integrated Haematology and Malignancy Diagnostic Service-Haematology, Great Ormond Street Hospital for Children, London, United Kingdom.ORCID 0000-0002-2650-2848
Bing M ZhangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA.ORCID 0000-0002-1750-1659
Nichola CooperCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.ORCID 0000-0002-9845-8292
Imperial College London · GBPalo Alto University · USGreat Ormond Street Hospital · GBCornell University · USImperial College Healthcare NHS Trust · GBShandong First Medical University · CNStanford University · USSt George's, University of London · GBTaibah University · SAUniversity College London · GB

Funding

TUMOR SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN BONE MARROW TRANSPLANTATIONP01CA049605 · NCI · STANFORD UNIVERSITY · PI David B. Miklos · 1989 to 2026
$73.3M
British Heart Foundation PG/17/22/32868British Heart Foundation RG/18/3/33405NCI NIH HHS P01 CA049605
6 · The paper itself

Abstract

Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multidimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterized patients with ITP and compared them with age-matched controls using immunophenotyping, next-generation sequencing of T-cell receptor (TCR) genes, single-cell RNA sequencing, and functional T-cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon gamma, tumor necrosis factor α, and granzyme B, defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the TCR showed expanded T-cell clones in patients with ITP. T-cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon gamma, and trigger platelet activation and apoptosis via the TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP.

Indexed as

Purpura, Thrombocytopenic, IdiopathicAdultCD8-Positive T-LymphocytesClone CellsHumansInterferon-gammaReceptors, Antigen, T-CellInterferon-gammaReceptors, Antigen, T-Cell

Identifiers

PMID36749920
PMCPMC10329190
OpenAlexW4319339586

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.