The Plasma Level of Interleukin-1β Can Be a Biomarker of Angiopathy in Systemic Chronic Active Epstein-Barr Virus Infection

Ayaka Ohashi; Yu Uemura; Mayumi Yoshimori; Naomi Wada; Ken-Ichi Imadome; Kazuo Yudo; Takatoshi Koyama; Norio Shimizu; Miwako Nishio; Ayako Arai

doi:10.3389/fmicb.2022.874998

The Plasma Level of Interleukin-1β Can Be a Biomarker of Angiopathy in Systemic Chronic Active Epstein-Barr Virus Infection

Front Microbiol. 2022 Apr 6:13:874998. doi: 10.3389/fmicb.2022.874998. eCollection 2022.

Authors

Ayaka Ohashi^{1

2

3}, Yu Uemura³, Mayumi Yoshimori⁴, Naomi Wada⁵, Ken-Ichi Imadome⁵, Kazuo Yudo¹, Takatoshi Koyama^{2

6}, Norio Shimizu⁷, Miwako Nishio², Ayako Arai^{3

4}

Affiliations

¹ Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.
² Department of Laboratory Molecular Genetics of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
³ Division of Hematology and Oncology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
⁴ Department of Hematological Therapeutics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
⁵ Department of Advanced Medicine for Viral Infections, National Center for Child Health and Development, Tokyo, Japan.
⁶ Department of Hematology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
⁷ Center of Stem Cell and Regenerative Medicine, Advanced Multidisciplinary Research Cluster, Institute of Research, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Abstract

Systemic chronic active Epstein-Barr virus infection (sCAEBV) is an EBV-positive T- or NK-cell neoplasm revealing persistent systemic inflammation. Twenty-five percent of sCAEBV patients accompany angiopathy. It is crucial to clarify the mechanisms of angiopathy development in sCAEBV because angiopathy is one of the main causes of death. Interleukin-1β (IL-1β) is reported to be involved in angiopathy onset. We investigated if IL-1β plays a role as the inducer of angiopathy of sCAEBV. We detected elevated IL-1β levels in four out of 17 sCAEBV patient's plasma. Interestingly, three out of the four had clinically associated angiopathy. None of the other patients with undetectable level of IL-1β had angiopathy. In all patients with high plasma levels of IL-1β and vascular lesions, EBV-infected cells were CD4-positive T cells. In one patient with high plasma IL-1β, the level of IL-1β mRNA of the monocytes was 17.2 times higher than the level of the same patient's EBV-infected cells in peripheral blood. In Ea.hy926 cells, which are the models of vascular endothelial cells, IL-1β inhibited the proliferation and induced the surface coagulation activity. IL-1β is a potent biomarker and a potent therapeutic target to treat sCAEBV accompanying angiopathy.

Keywords: IL-1β; angiopathy; coagulation; monocytes; sCAEBV.