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Determination of Clinical Cellular Immune Markers in Women with Recurrent Pregnancy Loss

Authors

  • Sung Ki Lee,

    1. Department of Obstetrics and Gynecology, College of Medicine, Konyang University, Daejeon, Korea
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    • These authors equally contributed to this study.

  • Baeg Ju Na,

    1. Department of Preventive Medicine, College of Medicine, Konyang University, Daejeon, Korea
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    • These authors equally contributed to this study.

  • Jee Yun Kim,

    Corresponding author
    • Department of Obstetrics and Gynecology, College of Medicine, Konyang University, Daejeon, Korea
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    • These authors equally contributed to this study.

  • Sung Eun Hur,

    1. Department of Obstetrics and Gynecology, College of Medicine, Konyang University, Daejeon, Korea
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  • Millina Lee,

    1. Department of Obstetrics and Gynecology, College of Medicine, Konyang University, Daejeon, Korea
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  • Alice Gilman-Sachs,

    1. Department of Microbiology and Immunology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
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  • Joanne Kwak-Kim

    1. Department of Microbiology and Immunology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
    2. Department of Obstetrics and Gynecology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, Vernon Hills, IL, USA
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Correspondence

Joanne Kwak-Kim, Reproductive Medicine, Department of Obstetrics and Gynecology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, 830 West End Court, Suite 400, Vernon Hills, IL 60061, USA.

E-mail: joanne.kwakkim@rosalindfranklin.edu

Abstract

Problem

Dysregulated natural killer (NK) immunity and T-cell immunity are associated with recurrent pregnancy loss (RPL). We aim to define clinically relevant NK and T-cell parameters for RPL and determine their cutoff values.

Methods of study

Ninety-five women with RPL (>3) including 42 idiopathic and 53 known-etiology RPL, and 29 age-matched fertile controls were enrolled. Peripheral blood immunophenotype, NK cell cytotoxicity (NKC), and T-helper (Th) 1 and Th2 cytokine producing cell ratios (Th1/Th2) were measured using flowcytometry. The cutoff values were determined using Youden's J with likelihood ratio (LR) >2.

Results

Natural killer cell percentage and NKC, TNF-α+ Th1 cells, and TNF-α/IL-10 producing Th1/Th2 cell ratio were significantly higher in idiopathic RPL than controls. By the area under the curve (AUC) analysis, NK cell percentage (AUC = 0.691), NKC (AUC = 0.649), TNF-α+ Th1 cells (AUC = 0.681) and Th1/Th2 cell ratio (AUC = 0.660) were highly specific for RPL. The cutoff values for NK cell percentage, NKC (E:T cell ratio 25:1), and TNF-α/IL-10 producing Th1/Th2 cell ratio are 16.1, 23.8, and 36.2%, respectively. Seventy-six percent of idiopathic RPL showed at least one of more immune abnormalities by these criteria.

Conclusion

Differences in NK cell percentages, NKC and Th1/Th2 cell ratio differentiated RPL from fertile controls.

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