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Children With Kawasaki Disease Are Not Infected With Epstein-Barr Virus

Fuse, Shigeto MD, PhD; Fujinaga, Emiko MD; Mori, Toshihiko MD, PhD; Hotsubo, Tomoyuki MD, PhD; Kuroiwa, Yuki MD, PhD; Morii, Maiko MD

The Pediatric Infectious Disease Journal: March 2010 - Volume 29 - Issue 3 - p 286-287
doi: 10.1097/INF.0b013e3181c3f111
Letters to the Editor

Department of Pediatrics NTT East Japan Sapporo Hospital Sapporo, Hokkaido, Japan

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To the Editors:

From 2004 to 2008, 157 patients with confirmed Kawasaki disease (KD) and 650 control patients with suspected KD were admitted to our hospital. The seroprevalence of Epstein-Barr virus (EBV) viral capsid antigen (VCA)-IgG in these subjects was determined using EBV ELISA kits.

There were only 7 among the 157 patients with KD who were EBV-seropositive, and all were less than 6 months old. In the control patients, the seropositivity rate was 0.69 in infants less than 6 months old and 0.04 in infants between 7 and 11 months old. The seropositivity rates in the control group were 0.09 at 1 year, 0.32 at 2 to 3 years, 0.34 at 4 to 6 years, 0.57 at 7 to 10 years, and 0.82 at 11 to 15 years. While the EBV seropositivity rates were not significantly different between the KD patients and control patients less than 11 months old (P = 0.22 and 1.00), the rates in 1-year-old, 2- to 3-year-old, and 4- to 6-year-old children with KD were significantly lower than those in control patients of the corresponding age groups (P = 0.04, 0.00000, and 0.00001).

EBV infection in humans continues to exist as a latent or persistent infection of B cells during almost all of a human life. We reconfirmed that KD patients were EBV-seronegative at the onset of KD, consistent with our finding in a previous study.1 The susceptibility of KD was related with EBV-seronegativity. In other words, EBV infection to B cell may have a defensive factor for the onset of KD. The defensive mechanism from KD was anticipated that EB viral proteins, such as viral interleukin-10, homologous human interleukin-10, which shares functions in the regulation of immune and inflammatory responses in B-cell,2 may modulate the host-organism interactions and immune regulation.

We also demonstrated in this study that the serum EBV VCA-IgG positivity rate was only 34% among 4- to 6-year-old Japanese children as control subjects. The seropositivity rate among children 5 to 7 years old was 100% in 1969,3 88% in 1975–1989, 78% in 1990–1994, 62% in 1995–1999, and less than 50% in 2006.4 Over the last 40 years, the EBV-seropositivity rate in Japanese children has decreased to one-third.

Decreasing prevalence of EBV infection in Japanese children may be responsible for the emergence of KD and the steady increase of KD patients from the 1960s.5

The etiology and pathogenesis of KD in Japanese children without evidence of EBV infection remain to be clarified. Further investigation of the differences in the immune responses including the B-cell system, in the presence and absence of EBV infection is necessary.

Shigeto Fuse, MD, PhD

Emiko Fujinaga, MD

Toshihiko Mori, MD, PhD

Tomoyuki Hotsubo, MD, PhD

Yuki Kuroiwa, MD, PhD

Maiko Morii, MD

Department of Pediatrics NTT East Japan Sapporo Hospital Sapporo, Hokkaido, Japan

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1. Iwanaga M, Takada K, Osato T, et al. Kawasaki disease and Epstein-Barr virus [letter]. Lancet. 1981;1:938–939.
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3. Hinuma Y, Ota-Hatano R, Suto T, et al. High incidence of Japanese infants with antibody to a herpes-type virus associated with cultured Burkett lymphoma cells. Jpn J Microbiol. 1969;13:309–311.
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5. Kawasaki T, Kosaki F, Okawa S, et al. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics. 1974;54:271–276.
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