A Molecular Approach to the Etiology of Kawasaki Disease

Prompted by the recent discovery of two new orphan viruses, specifically GBV-C/HGV and TTV, in conjunction with increasing consensus implicating Chlamydia pneumoniae infection in atherosclerotic cardiovascular disease, we utilized polymerase chain reactions (PCR) to determine if Kawasaki disease (KD) could be etiologically linked with these microbial agents.  In addition, we tested these samples from KD patients for evidence of infection with parvovirus B19 and human herpesvirus 8, a gamma herpesvirus causing Kaposiâs sarcoma.  Blood and urine were collected from 123 patients (55 females, 68 males; age range, 1 month to 8 years; mean age, 2.4 years) who presented with KD at the Kapiâolani Medical Center for Women and Children between 1980 and 1999.  RNA and DNA were extracted from plasma, serum or whole blood for amplification of GBV-C/HGV, TTV, parvovirus B19, HHV 8 and C. pneumoniae, and sera were screened for IgG and IgM antibodies against parvovirus B19 by enzyme immunoassay.  Nearly 60% (26 of 46) of KD patients had either IgG or IgM antibodies against parvovirus B19, whereas only 5 of 46 (11%) had both IgG and IgM antibodies.  Patients in the 0-2 year age group had the highest age-specific seroprevalence of IgG or IgM antibodies against parvovirus B19.  However, PCR data showed that only two of the 46 patients examined harbored parvovirus B19 DNA, indicating that there was no evidence of the virus circulating within the blood at the time of specimen collection.

Similarly, we were unable to amplify cryptic HHV-8 sequences from any of the 77 KD patients tested; and TTV DNA sequences and GBV-C/HGV RNA sequences were detected by PCR in only two of 77 KD patients; and we were unable to amplify C. pneumoniae cryptic sequences from the peripheral blood mononuclear cells or urine samples of 26 KD patients.  Therefore, we were unable to establish an etiologic link between infection with any of the above-mentioned microbes and KD.  However, these data do not definitively exclude the possibility that KD has an infectious etiology.  One explanation could be that a previously undescribed microbial agent may be the cause of KD.  Also, it could be indicative that the microbial agent had been cleared from the body at the time of specimen collection.  Sensitive molecular techniques, including representational difference analysis, are currently being employed to identify the infectious agent of KD.

Chua, P.K., Nerurkar, V.R., Yu, Q., Woodward, C.L., Melish, M.E., and Yanagihara, R.:  No etiological association between Kawasaki syndrome and infection with parvovirus B19, human herpesvirus 8, TT Virus, GB virus C/hepatitis G virus or Chlamydia pneumoniae.  Pediatric Infectious Diseaess Journal 1999 (submitted).

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