The Role Of T Cell CD40L In The Pathogenesis Of Kawasaki Disease

Background: Kawasaki disease (KD) is an acute, systemic vasculitis of unknown origin that affects primarily infants and young children. In untreated patients, there is a risk of coronary artery lesions (CAL) in the subacute and convalescent phase of the disease. KD is one of the most common causes of acquired heart disease in children. The etiology of this disease is still unknown. It is accepted that abnormal activation of T cell plays a central role in the pathogenesis of KD. High-dose intravenous immunoglobulin (IVIG) treatment within the first 10 d of the disease significantly reduces the frequency of CAL, which suggests over activation of immune system in the acute phase of KD is very important for CAL. Recently, it was hypothesized that Kawasaki disease was a risk factor for atherosclerosis in later life. Basic research found CD40 ligand (CD40L) on T cell had effects on inflammation by interaction with CD40 on target cells. And clinical research indicated thatthe CD40-CD40L pathway was a key element in atherosclerosis. Objective: The aim of the study was to investigate the role of T cell CD40L in the pathogenesis of vasculitis and CAL in KD.1 To investigate the probable role of T cell CD40L in KD by observing the expression of CD40L on T cell in KD patient pre and post IVIG. 2 To investigate if plasma levels of soluble E-selectin (sE-selectin),soluble intercellular adhesion molecule 1 (sICAM-1) and matrix metalloproteinase 9 (MMP9) can be used to reflect the degree of vasculitis of Kawasaki disease and if they can be used as predicators of CAL.3 To investigate the effect of T cell CD40L in Kawasaki disease by correlation analysis between T cell CD40L and sE-selectin, sICAM-1 and MMP9 in the acute phase of KD.Methods: 1 The expressions of CD40L on T cells were detected in 20 KD patients pre and post IVIG, and 19 normal children by 2-color flow cytometry.2 The levels of plasma sE-selectin, sICAM-1 and MMP9 were detected by ELISA in 25 KD patients (including 20 patients mentioned above) pre and post IVIG and 19 normal children.3 Correlation analysis was done between the expression of CD40L on T cell and plasma sE-selectin, sICAM-1 and MMP9 in the acute phaseof KD patients.Results: 1 The percentage of T cells expressing CD40L and the mean fluorescence intensity of positive cells (MFI) of T cell CD40L expression were significantly higher compared pre-IVIG with post-IVIG in KD patients (27.91%±16.88% vs. 23.09%±16.22%(P<0.05), 11.74±8.35 vs. 8.18±6.71, (P<0.01)). The expressions of T cell CD40L in KD patients were prolonged compared with normal control.2 The percentage of cells positive for CD40L and MFI for CD40L in 2 KD patients with CAL (54.62% and 32.80,47.25% and 18.40 , respectively) were higher than patients without CAL in the acute phase.3 The plasma levels of sE-selectin (205.70±88.99ng/ml vs. 135.85±39.54ng/ml) and sICAM-1(465.16±189.90ng/ml vs. 316.12±78.24ng/ml) in the acute phase of KD patients were elevated in comparison to normal children (P<0.05). Paired analysis of KD patients pre and post IVIG revealed lowered levels of sICAM-1(465.16±189.90ng/ml vs. 417.78±163.05ng/ml, P<0.05) and MMP9 (180.00±119.08ng/ml vs. 121.13±44.54ng/ml, P<0.05). In the acute phase of KD, the plasma levels of sICAM-1(r=0.732, P<0.01) and MMP9(r=0.548, P<0.01) were related to the levels of sE-selectin. 4 The plasma levels of sE-selectin, sICAM-1 and MMP9 in 2 patients with CAL (277.5ng/ml, 489.4ng/ml, and 176.4ng/ml; 127.5ng/ml, 396.2ng/ml, and 105.6ng/ml, respectively) were not different frompatients without CAL in the acute phase. 5 Correlation was not found between T cell CD40L and plasma sE-selectin, sICAM-1 and MMP9 (P>0.05).Conclusions: 1 The expression of CD40L on T cell is increased and prolonged in the acute phase of KD, it may probably play a role in the pathogenesis of vasculitis and coronary artery lesions of KD. 2 The plasma levels of sE-selectin, sICAM-1 and MMP9 may be used to reflect the degree of vasculitis of KD...