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Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection

Marcus Buggert, Juliet Frederiksen, Kajsa Noyan, Jenny Svärd, Babilonia Barqasho, Anders Sönnerborg, Ole Lund, Piotr Nowak and Annika C. Karlsson
J Immunol February 3, 2014, 1302596; DOI: https://doi.org/10.4049/jimmunol.1302596
Marcus Buggert
*Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, S-141 86 Stockholm, Sweden;
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Juliet Frederiksen
†Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark; and
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Kajsa Noyan
*Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, S-141 86 Stockholm, Sweden;
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Jenny Svärd
‡Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
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Babilonia Barqasho
*Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, S-141 86 Stockholm, Sweden;
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Anders Sönnerborg
*Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, S-141 86 Stockholm, Sweden;
‡Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
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Ole Lund
†Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark; and
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Piotr Nowak
*Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, S-141 86 Stockholm, Sweden;
‡Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
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Annika C. Karlsson
*Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, S-141 86 Stockholm, Sweden;
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Abstract

HIV disease progression is characterized by numerous pathological changes of the cellular immune system. Still, the CD4 cell count and viral load represent the laboratory parameters that are most commonly used in the clinic to determine the disease progression. In this study, we conducted an interdisciplinary investigation to determine which laboratory parameters (viral load, CD4 count, CD8 count, CD4 %, CD8 %, CD4/CD8) are most strongly associated with pathological changes of the immune system. Multiparametric flow cytometry was used to assess markers of CD4+ and CD8+ T cell activation (CD38, HLA-DR), exhaustion (PD-1, Tim-3), senescence (CD28, CD57), and memory differentiation (CD45RO, CD27) in a cohort of 47 untreated HIV-infected individuals. Using bioinformatical methods, we identified 139 unique populations, representing the “combined T cell pathogenesis,” which significantly differed between the HIV-infected individuals and healthy control subjects. CD38, HLA-DR, and PD-1 were particularly expressed within these unique T cell populations. The CD4/CD8 ratio was correlated with more pathological T cell populations (n = 10) and had a significantly higher average correlation coefficient than any other laboratory parameters. We also reduced the dimensionalities of the 139-unique populations by Z-transformations and principal component analysis, which still identified the CD4/CD8 ratio as the preeminent surrogate of combined T cell pathogenesis. Importantly, the CD4/CD8 ratio at baseline was shown to be significantly associated with CD4 recovery 2 y after therapy initiation. These results indicate that the CD4/CD8 ratio would be a suitable laboratory predictor in future clinical and therapeutic settings to monitor pathological T cell events in HIV infection.

Footnotes

  • This work was supported by the Swedish Research Council (Grants K2010-56X-20345-04-3 and K2014-57X-22451-01-5), the Karolinska Institutet, the Swedish Physicians against AIDS Research Foundation (Grant FOa2011-0021), and the Magnus Bergvalls Foundation.

  • The online version of this article contains supplemental material.

  • Received September 27, 2013.
  • Accepted December 26, 2013.
  • Copyright © 2014 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 208 (10)
The Journal of Immunology
Vol. 208, Issue 10
15 May 2022
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Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection
Marcus Buggert, Juliet Frederiksen, Kajsa Noyan, Jenny Svärd, Babilonia Barqasho, Anders Sönnerborg, Ole Lund, Piotr Nowak, Annika C. Karlsson
The Journal of Immunology February 3, 2014, 1302596; DOI: 10.4049/jimmunol.1302596

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Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection
Marcus Buggert, Juliet Frederiksen, Kajsa Noyan, Jenny Svärd, Babilonia Barqasho, Anders Sönnerborg, Ole Lund, Piotr Nowak, Annika C. Karlsson
The Journal of Immunology February 3, 2014, 1302596; DOI: 10.4049/jimmunol.1302596
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