Immunologic Abnormalities in Kawasaki Disease and the Effect of Intravenous Immunoglobulin

ABSTRACT

PURPOSE: It has been suggested that immunologic abnormalities play a role in the pathogenesis of vascular injury in Kawasaki disease and the immunologic abnormalities could be regulated by high-dose intravenous immunoglobulin(IVIG). We investigated the peripheral blood lymphocyte subsets, the serum levels of interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-alpha) and the effect of high- dose IVIG(400 mg/kg/day for 5 days) on these factors during acute stage of Kawasaki disease. METHODS: Thirty patients, aged 4 months to 5 years, who met the diagnostic criteria for Kawasaki disease were enrolled in this study. Patients were divided into two groups, Kawasaki disease with coronary vascular lesion(KD-CVL) and without coronary vascular lesion (KD-NCVL). Percentages of peripheral blood lymphocyte subsets were measured by flow-cytometry and the serum levels of IL-6 and TNF-alpha were measured by ELISA on 1 day before and 1 day after IVIG administration and compared with normal control group(n=15). RESULTS: The results were as follows 1) Before IVIG administration, the percentages of CD3+ lymphocyte and CD8+ lymphocyte in both KD-CVL and KD-NCVL were significantly lower than those in control group. The percentages of CD19+ lymphocyte and CD4+/CD8+ ratio in both groups were significantly higher than those in control group. There was no significant differences between the percentages of CD4+ lymphocyte in both groups and that in control group. 2) After IVIG administration, the percentages of CD3+ lymphocyte and CD8+ lymphocyte in both KD-CVL and KD-NCVL were significantly increased. The percentages of CD19+ lymphocyte and CD4+/CD8+ ratio in both KD-CVL and KD-NCVL were significantly decreased. The percentages of CD4+ lymphocyte were not changed. 3) Before IVIG administration, the detection rate of serum IL-6 and TNF-alpha in both groups was significantly higher than that in control group. After IVIG administration, the detection rate of serum IL-6 in both groups was still higher than that in control group. In KD-CVL, the detection rate of serum TNF-alpha was still higher than that in control group but there was no significant difference between the detection rate of TNF-alpha in KD-NCVL and that in control group. 4) Before IVIG administration, the serum levels of IL-6 in Kawasaki disease were significantly higher than that in control group but there was no significant difference between those in KD-CVL and KD-NCVL. After IVIG administration, the serum level of IL-6 in KD-CVL was not decreased. In KD-NCVL, it was decreased significantly but it was still higher than that in control group after IVIG administration. Before IVIG administration, the serum levels of TNF-alpha in Kawasaki diseases were significantly higher than that in control group and that in KD-CVL was significantly higher than that in KD-NCVL. After IVIG administration, the serum level of TNF-alpha in KD-CVL was not decreased but in KD-NCVL, it was decreased significantly to the level of control group. CONCLUSIONS: Immunologic abnormalities including decreased percentage of CD3+ lymphocyte, CD8+ lymphocyte, increased percentage of CD19+ lymphocyte and CD4+/ CD8+ ratio and increased levels of IL-6 and TNF-alpha were noted in the acute stage of Kawasaki diseases. But there were no difference of above immunologic abnormalities between KD-CVL and KD-NCVL. After IVIG administration, the abnormal percentages of peripheral blood lymphocyte subsets were changed to normal but in the cases of IL-6 and TNF-alpha, the levels were continuously elevated except TNF-alpha in KD-NCVL. Therefore the immunologic abnormalities including abnormal percentages of peripheral blood lymphocyte subsets and increased production of IL-6 and TNF-alpha might be involved in the pathogenesis of Kawasaki disease. And IVIG has some effects on the change of these kinds of immunologic abnormalities.