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Clinical and Diagnostic Laboratory Immunology, January 2004, p. 123-130, Vol. 11, No. 1
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.1.123-130.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Maintenance of Serum Immunoglobulin G Antibodies to Epstein-Barr Virus (EBV) Nuclear Antigen 2 in Healthy Individuals from Different Age Groups in a Japanese Population with a High Childhood Incidence of Asymptomatic Primary EBV Infection

Shizuko Harada,1 Yoshio Kamata,1 Yasuyuki Ishii,1 Hiroyuki Eda, Ryo Kitamura,1 Maya Obayashi,1 Sayuri Ito,1 Fumihiko Ban,1 Jun Kuranari,1 Haruhiko Nakajima,1 Tomoko Kuze,1 Masao Hayashi,1 Nobuhiko Okabe,2,3 Hidenobu Senpuku,4 Nobuyuki Miyasaka,5 Yoshiko Nakamura,6 Hirokazu Kanegane,7 and Kazuo Yanagi1*

Herpesvirus Laboratory, Department of Virology I,1 Infectious Disease Surveillance Center,2 Department of Bacteriology I, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640,4 Department of Pediatrics, Kanagawa Prefecture Nursing School Hospital, Yokohama City, Kanagawa 235-0022,3 Department of Autoimmune Diseases and Rheumatology, School of Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-0034,5 Department of Pathology, Showa Medical School Fujigaoka Hospital, Fujigaoka 1-30, Aoba-ku, Yokohama City, Kanagawa 227-0043,6 Department of Pediatrics, School of Medicine, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama City, Toyama 930-0152, Japan7

Received 24 July 2003/ Returned for modification 16 October 2003/ Accepted 7 November 2003

Immunoglobulin G (IgG) antibodies to Epstein-Barr virus (EBV) nuclear antigens 2 and 1 (EBNA-2 and EBNA-1, respectively) were studied using sera from healthy individuals of a population with a high incidence of asymptomatic primary EBV infections during infancy or childhood in Japan. Two CHO-K1 cell lines expressing EBNA-2 and EBNA-1 were used for anticomplement and indirect immunofluorescence assays. The positivity rate for EBNA-2 IgG rose in the 1- to 2-year age group, increased and remained at a plateau (~45%) between 3 and 29 years of age (3- to 4-, 5- to 9-, 10- to 14-, and 15- to 29-year age groups), and then reached 98% by age 40 (>=40-year age group). Both seropositivity for EBNA-1 and seropositivity for EBNAs in Raji cells (EBNA/Raji) were detected in the 1- to 2-year age group, remained high, and finally reached 100% by age 40. The geometric mean titer (GMT) of EBNA-2 IgG reached a plateau in the 5- to 9- and 10- to 14-year-old groups and remained elevated in the older age groups (15 to 29 and >=40 years). The GMT of EBNA-1 IgGs increased to a plateau in the 1- to 2-year-old group and remained unchanged in the older age groups. The GMT of EBNA/Raji IgGs also reached a plateau in the 1- to 2-year-old group, remained level throughout the 3- to 14-year age groups, and decreased in the 15- to 29-year-olds. EBNA-2 IgGs emerged earlier than EBNA-1 IgGs in 8 of 10 patients with infectious mononucleosis, who were between 1 and 27 years old, and declined with time in three of eight cases. These results suggest that EBNA-2 IgG antibodies evoked in young children by asymptomatic primary EBV infections remain elevated throughout life, probably because of reactivation of latent and/or exogenous EBV superinfection.


* Corresponding author. Mailing address: Herpesvirus Laboratory, Department of Virology I, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. Phone and fax: 81-3-5285-1180. E-mail: kyanagi{at}nih.go.jp.


Clinical and Diagnostic Laboratory Immunology, January 2004, p. 123-130, Vol. 11, No. 1
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.1.123-130.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.