Temporal Dynamics of Serum Perforin and Granzymes in Three Different Clinical Stages of Virus-Induced Severe Fever with Thrombocytopenia Syndrome

Sukhyun Ryu Department of Preventive Medicine, Konyang University College of Medicine, Daejeon, South Korea;

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Jin Kyeong Choi Department of Immunology, Jeonbuk National University Medical School, Jeonju, South Korea;

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Chiara Achangwa Department of Preventive Medicine, Konyang University College of Medicine, Daejeon, South Korea;

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Soojung Cho Department of Preventive Medicine, Konyang University College of Medicine, Daejeon, South Korea;

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Joo-Hee Hwang Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, South Korea;
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea;

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Jeong-Hwan Hwang Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, South Korea;
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea;

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Niels Bovenschen Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands;
Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands;

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Chang-Seop Lee Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, South Korea;
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea;
Department of Medical Science, Jeonbuk National University Medical School, Jeonju, South Korea

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ABSTRACT.

Virus-induced severe fever with thrombocytopenia syndrome (SFTS) induces a cell-mediated immune response that likely contributes to virus control in SFTS patients. To identify the temporal changes of the cell-mediated immune response, we investigated the changes in serum levels of perforin and granzymes at early periods after illness onset in SFTS patients. We analyzed 32 SFTS patients and compared the temporal patterns of serum perforin and granzyme A and B to that of 20 healthy control adults using the Mann-Whitney U test. Compared with healthy controls, the mean level of perforin was significantly reduced by 81% (P < 0.01) during the first week after illness onset, whereas granzyme B significantly increased by 4.6-fold (P = 0.02) in the first week after illness onset and decreased to normal afterward. During the study period, there was no significant difference in serum perforin and granzyme. These findings indicate that perforin and granzyme B in serum can be considered possible serologic markers that reflect the clinical stage of SFTS. Additional study is warranted for tracking circulating perforin and granzyme in different ages and for an extended period after illness onset.

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Author Notes

Address correspondence to Chang-Seop Lee, Department of Internal Medicine, Jeonbuk National University Medical School, 20 Geonjiro, Deokjin-gu, Jeonju, 54907 South Korea. E-mail: lcsmd@jbnu.ac.kr

Financial support: This research was supported by the Biomedical Research Institute of Jeonbuk National University Hospital and by the Basic Science Research Programs (NRF-2015R1D1A1A01060251 and 2018R1D1A3B07049557) of the National Research Foundation of Korea, which is funded by the Ministry of Education.

The data underlying this article will be shared on reasonable request to the corresponding author. All study participants provided written informed consent, and all study procedures were approved by the Institutional Review Board (IRB) of Jeonbuk National University Hospital (IRB registration number 2019-06-020).

Authors’ addresses: Sukhyun Ryu, Chiara Achangwa, and Soojung Cho, Department of Preventive Medicine, Konyang University College of Medicine, Daejeon, South Korea, E-mails: gentryu@onehealth.or.kr, ciaraacha@gmail.com, and 22531518@konyang.ac.kr. Jin Kyeong Choi, Department of Immunology, Jeonbuk National University Medical School, Jeonju, South Korea, E-mail: jkchoi@jbnu.ac.kr. Joo-Hee Hwang and Jeong-Hwan Hwang, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, South Korea, and Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea, E-mails: zany78@naver.com and smilehwang77@hanmail.net. Niels Bovenschen, Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands, and Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands, E-mail: n.bovenschen@umcutrecht.nl. Chang-Seop Lee, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, South Korea, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea, and Department of Medical Science, Jeonbuk National University Medical School, Jeonju, South Korea, E-mail: lcsmd@jbnu.ac.kr.

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