Expression of Apoptosis Inhibitor Genes and Resistance of T Cells to Apoptosis in the Early Acute Phase of Kawasaki Disease

Abstract

Objective. The acute phase of Kawasaki disease (KD) is characterized by the deregulated production of proinflammatory cytokines and chemokines by PBMC. We studied the activation induced cell death of the peripheral blood T cells and the expression of the apoptosis-related genes during the course of the disease. Methods. Heparinized blood was obtained from 63 patients, 2-4d (Group A, n=25), 5-7d (Group B, n=29), 8-11d (Group C, n=9), 12-14d (Group D, n=9), and >15d (Group E, n=13) after the onset of fever. PBMC were isolated 24h after blood drawing and stained with anti-CD3 antibody and Annexin V followed by the flow cytometry analysis. The expression of the apoptosis-related genes was studied on PBMC obtained during the acute (<6d) and convalescent (>11d) phase of KD by RT-PCR. Results. The percentage of apoptotic T cells was not increased in the early acute phase (Group A, 13.3%), but gradually increased during the subacute phase with the peak value in the Group C (26.2%, p=0.0002 by Fisher's PLSD). After IVGG therapy, the percentage of apoptotic T cells was significantly increased (15.2% vs. 20.2%, p=0.02 by unpaired t test). The expression of the anti-apoptotic protein genes such as FLICE-like inhibitory protein (FLIP), X-linked inhibitor of apoptosis protein (XIAP), and Bcl-XL was significantly elevated during the acute phase compared with the convalescent phase of KD. Conclusion. The enhanced expression of the apoptosis inhibitory proteins during the early acute phase of KD may prevent the induction of activation induced cell death of PBMC and contribute to the sustained production of proinflammatory cytokines during the acute illness.