A Study of Epstein-Barr Virus, and Human Leukocyte Antigen Typing in Children with Acute Infectious Mononucleosis

PURPOSE: The Epstein-Barr virus(EBV), gamma herpesvirus, is an important pathogen that is widespread around the world. The EBV causes various diseases depending on the geographic location, and on the immunity or the premorbid condition of the person exposed to EBV. To evaluate EBV typing may be the most important step to figure out the pathogenesis of EBV associated diseases, and we need to re-evaluate the pathologic role of human leukocyte antigen(HLA) in developing Epstein-Barr virus associated acute infectious mononucleosis by using newly developed methods. METHODS: This study included 24 children(age range : 6 to 13 years), serologically confirmed with acute infectious mononucleosis. The control group for the HLA type consisted of 200 age-matched healthy children. To classify HLA I, modified ARMs-PCR was used, while modified PCR-SSOP was utilized in typing of HLA II. Also, we performed EBV typing in study patients by using a one-step PCR. RESULTS: The results of HLA types : In HLA class I, HLA-A24 was positive in 69 of 200 healthy children and positive in 14 of 24 patients in the study group(relative risk : 3.5724, chi-square; 5.26, P<0.05). In HLA class II, HLA-DRB1*07 was detected in 18 of 200 healthy children, and eight of 24 patients in the study group(relative risk; 506173, chi-square; 9.73, P<0.01). The results of EBV types : In the research group, 20(83.8%) of 24 patients were shedding type A virus, while 4(16.7%) were type B. CONCLUSION: We conclude that development of infectious mononucleosis may be associated with HLA types, and these results suggest that acute infectious mononucleosis could have hereditary traits. And we confirm that type A EBV is highly prevalent in patients with acute infectious mononucleosis in Korea. Also, our results suggest that further large scale studies, including adult groups, regarding the association between pathogenesis of EBV with HLA-DP or HLA-DQ will be warranted.

Typing of Epstein-Barr Virus in Children with Febrile Illness and Malignancies / 감염

BACKGROUND: The Epstein-Barr virus (EBV) is a human DNA herpesvirus that causes worldwide spread. Primary infection of EBV in early childhood is often subclinical, and more than 90% of children older than five years of ages are seropositive for EBV in Korea. Two types of EBV have been described which differ in their geographical distributions and associated diseases. Variable diseases including many malignancies are associated with EBV infections. And the pathogenesis of EBV associated diseases are very complicated. To study EBV typing in EBV associated diseases could be the first step to find out the pathogenesis of EBV associated diseases, and to confirm the altered reactivation and typing of EBV under various disease conditions may be indirectly helpful to understand the pathogenesis of EBV associated diseases. In this aspect, we performed this study. METHODS: The study group included 90 children (age range 1 to 15 years) with febrile illness and malignancies who had serologic evidence of previous EBV infection. Sixty-two cases of the study group had febrile illness and 28 cases had malignancies. Febrile illness groups were classified into bacterial infection, non-bacterial infection and Kawasaki disease. The control group included 62 healthy children in the range of 5 to 15 years of age. Mouth washing samples were taken and two types, EBV A and B were identified by using one-step PCR. B95-8 cells (type A) and Jijoye cells (type B) were used as positive controls, and K-562 cells was used as a negative control. RESULTS: The results were as follows; Eleven (17.7%) of the 62 healthy children had EBV DNA in throat washings : of these, 8 (72.7%) were shedding type A virus, and 3 (27.3%) type B. EBV was detected in 12 (57%) of the 21 patients with bacterial infection : 7 (58.3%) had A type, 2 (16.7%) B type, and 3 (25%) both types. 23 (79.3%) of the 29 patient with non-bacterial infection had EBV DNA in throat washing: of these, 15 (65.2%) had A type, 4 (17.4%) B type, and 4 (17.4%) both types. Two (16.7%) of the 12 patients with Kawasaki disease had EBV DNA in throat washing; all of them were type A. EBV was detected in 15 of the 28 children with malignancies : 11 (73.3%) had only type A, 2 (13.3%) type B, and 2 (13.3%) both types. Overall, the seropositive rate of study group was significantly higher than that of control group. But, there was no significant difference in seropositive rate between febrile illness and malignancies. Both the seropositive rates in the bacterial infection and non-bacterial infection groups were significantly higher than that of Kawasaki disease group (respectively P<0.001, P<0.001). CONCLUSION: We have the facts and suggestions as followings; We reconfirm that type A EBV is highly dominant and no mixed infection in Korean healthy children. The EBV excretion rate in children with febrile illness or malignancies was about 3-fold higher than that in healthy children, and coinfection with type A and B was seen in both study group. These results suggest that EBV reactivation may be increased in the status of immunologic alteration, induced by diseases. By contrast, EBV reactivation may not be found in certain acute febrile illness like Kawasaki disease, in which immunologic alteration to reactivate EBV is not induced. We think that this study may provide the basis to figure out the pathogenesis of EBV associated diseases. But, The outcome of this study is incomplete and indirect to understand the host immune responses to EBV and pathognomic role according to EBV types. So, further large scaled studies of EBV subtyping using variable methods will be needed to investigate the pathogenesis of EBV associated diseases.