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T-large granular lymphocyte frequencies and correlates in disease states detected by multiparameter flow cytometry in pediatric and young adult population

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Abstract

T-large granular lymphocytes (T-LGL) characterized by dim CD5 staining, although not completely understood, have unique roles in the immune system. Expansion of peripheral blood (PB) clonal T-LGL populations is associated with various entities in adults. We have previously demonstrated clonal T-LGL proliferations in pediatric immune dysregulation/inflammatory/proliferative conditions. However, T-LGL populations have not been studied in broader spectrum pathologies. In this study we evaluated sizes and correlates of T-LGL populations in the pediatric and young adult populations with various disease states. Lymphocytes including T-LGL were investigated retrospectively by reviewing PB multiparameter flow cytometric data with various indications over a 4-year period. Associations with clinical, laboratory findings, and T-LGL population sizes were sought. Among 520 cases reviewed, 240 were females and 280 males with a mean age of 9 years (0–33 years); mean T-LGL population constituted 14% (1–67%) in PB T cells. There were significant differences between T-LGL and CD5-bright, regular T cells. T-LGL correlated with CD8 + /DR + (R = 0.570; P < 0.01) and CD8 + /CD11b + (R = 0.597; P < 0.01) expression, indicating activated cytotoxic phenotype. The highest average T-LGL were seen in bone marrow transplant recipients (23.7%), Evans syndrome (23.7%), lymphoma (20.6%), and acute EBV infection (20.4%) cases, all with underlying immune dysregulation pathologies. In pediatric and young adult patients with different clinical conditions, PB T-LGL constitute an average of 14% of the T cells and have a predominantly activated cytotoxic T cell phenotype. Higher relative presence was seen in cases with an immune dysregulation background. These results may serve as a reference for T-LGL research efforts.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study is supported partially by funds from Children’s Foundation and Kids Without Cancer Foundation.

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Authors and Affiliations

  1. Hematology/Oncology Flow Cytometry Laboratory, Children’s Hospital of Michigan, Detroit, MI, USA

    Manisha Gadgeel, Ishaq Al Kooheji, Batool Al-Qanber, Steven Buck & Süreyya Savaşan

  2. Department of Pediatrics, Central Michigan University College of Medicine, Mt Pleasant, USA

    Manisha Gadgeel, Ishaq Al Kooheji, Batool Al-Qanber & Süreyya Savaşan

  3. Division of Hematology/Oncology, Pediatric Transplant and Cellular Therapy Program, Children’s Hospital of Michigan, Detroit, MI, USA

    Süreyya Savaşan

Authors
  1. Manisha Gadgeel
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  2. Ishaq Al Kooheji
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  3. Batool Al-Qanber
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  4. Steven Buck
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  5. Süreyya Savaşan
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Contributions

M.G. performed flow cytometry data acquisition and wrote the manuscript; I.A. collected flow cytometry and clinical data and performed statistical analysis; B.A. collected flow cytometry and clinical data; S.B. performed flow cytometry data acquisition; S.S. planned the study, analyzed the results, revised the manuscript, and approved the final version.

Corresponding author

Correspondence to Süreyya Savaşan.

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Ethics approval

This research study was conducted retrospectively from data obtained for clinical purposes. We consulted extensively with the IRB of Wayne State University who determined that our study did not need ethical approval. An IRB official waiver of ethical approval was granted from the IRB of Wayne State University.

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The authors declare no competing interests.

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Accepted in abstract form titled “T-large granular lymphocyte frequencies and correlates in disease states detected by flowcytometry” for the American Society of Pediatric Hematology/Oncology (ASPHO) May 2023 annual meeting (Poster #305) and published in the Pediatric Blood and Cancer in June 2023 issue (Volume 70, Supplement 3).

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Gadgeel, M., Al Kooheji, I., Al-Qanber, B. et al. T-large granular lymphocyte frequencies and correlates in disease states detected by multiparameter flow cytometry in pediatric and young adult population. Ann Hematol 103, 133–140 (2024). https://doi.org/10.1007/s00277-023-05449-2

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  • DOI: https://doi.org/10.1007/s00277-023-05449-2

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