Clinical significance of anti-Epstein-Barr virus antibodies in systemic chronic active Epstein-Barr virus disease

Miwako Nishio; Minori Saito; Mayumi Yoshimori; Yuki Kumaki; Ayaka Ohashi; Eri Susaki; Ichiro Yonese; Megumi Sawada; Ayako Arai

doi:10.3389/fmicb.2023.1320292

Clinical significance of anti-Epstein-Barr virus antibodies in systemic chronic active Epstein-Barr virus disease

Front Microbiol. 2024 Jan 8:14:1320292. doi: 10.3389/fmicb.2023.1320292. eCollection 2023.

Authors

Miwako Nishio^#¹, Minori Saito^#¹, Mayumi Yoshimori¹, Yuki Kumaki¹, Ayaka Ohashi^{1

2}, Eri Susaki¹, Ichiro Yonese³, Megumi Sawada⁴, Ayako Arai^{1

3

5}

Affiliations

¹ Department of Hematology and Biophysical Systems Analysis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
² Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.
³ Department of Hematology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
⁴ Department of Nutrition, Tokyo Kasei University, Tokyo, Japan.
⁵ Department of Hematology and Oncology, St. Marianna University School of Medicine, Kanagawa, Japan.

^# Contributed equally.

Abstract

Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a rare and fatal neoplasm, involving clonally proliferating Epstein-Barr virus (EBV)-infected T cells or natural killer cells. Patients with sCAEBV have abnormal titers of anti-EBV antibodies in their peripheral blood, but their significance is unknown. We retrospectively investigated titers and their relationship with the clinical features of sCAEBV using the data collected by the Japanese nationwide survey. Eighty-four patients with sCAEBV were analyzed. The anti-EBV nuclear antigen (EBNA) antibody, targeting EBNA-expressing EBV-positive cells, was found in 87.5% of children (<15 years old), 73.7% of adolescents and young adults (15-39 years old), and 100% of adults (≥40 years old). Anti-EBNA antibody titers were significantly lower and anti-VCA-IgG antibody titers significantly higher in patients with sCAEBV than those in healthy controls (p < 0.0001). Patients with high anti-VCA-IgG and anti-early antigen-IgG antibody (antibodies against the viral particles) levels had significantly better 3-year overall survival rates than those with low titers, suggesting that patients with sCAEBV have a reduced immune response to EBV-infected cells.

Keywords: EBNA; VCA-IgG; anti-Epstein–Barr virus antibody; sCAEBV; systemic chronic active Epstein–Barr virus disease.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Practical Research Project for Rare/Intractable Diseases (18ek0109334h0001, 19ek0109334h0002, 20ek0109334h0003, 22ek0109609h0001, 23ek0109609h0002, 22ek0109612h0001, and 23ek0109612h0002) from the Japan Agency for Medical Research and Development (AMED).