The Study Of Expression Of Myeloid-related Protein-8 And -14, CD11b And MMP-9 In Kawasaki Disease

Objective:In order to investigate pathogenesis of vasculitis and CAL in Kawasaki disease (KD) and sought to laboratory diagnostic criteria and new targets for drug therapy for KD.we performed this study focusing on the Plasma MRP-8/MRP-14 heterodimers (Myeloid- Related Protein-8 and-14) and matrix metalloproteinase-9 (MMP-9) as well as MRP8mRNA, MRP14mRNA and Neutrphil adhesion molecule CD11bmRNA in Leukocyte in KD, to observe the change expression of MRP-8/MRP-14 heterodimers and Neutrphil adhesion molecule CD11b and matrix metalloproteinase -9 in KD.Methods:According to the criteria set in 2002 in Japan, 46 KD inpatients from July 2009 to December 2010 were objects of study. 25 febrile children with infection formed febrile groups. 20 healthy children formed health control groups. Refered to echocardiogram diagnostic standard, samples from KD patients were divided into two groups:coronary artery dilatation (CAD) groups (n=15) and cornary artery normal groups (n=31). Collecting peripheral venous blood in the actue and subacute stage of KD. MRP- 8/MRP- 14 and MMP-9 in Plasma were both detected with enzyme linked immunosorbent assay (ELISA). Gene expression of MRP-8, MRP-14 and CD11b in Leukocyte was analyzed by Semi-quantitative reverse transcription–polymerase chain reaction (RT-PCR).Result:1. The white blood cell count, neutrophil percentage and C-reactive protein were significantly higher in the acute KD than the sub-acute phase (P <0.0001).2. The plasma MRP-8/MRP-14 levels as well as mRNA expressions of MRP-8 and -14, CD11b in Leukocyte were significant higher in patients with acute KD than in febrile and healthy control patients (P<0.001), and decreased dramatically within subacute stage (P<0.001). But still higher than the febrile group and the healthy control group (P<0.05).3. The plasma MMP-9 level was significant higher in patients with acute KD than in febrile and healthy control patients (P<0.05), and decreased dramatically within subacute Stage (P<0.001). And no different from febrile and healthy control patients.4. The plasma MRP-8/MRP-14 and MMP-9 as well as mRNA expressions of MRP-8 and -14, CD11b in Leukocyte were significant higher in KD with coronary artery dilatation than in coronary artery normal patients (P<0.05).5. MRP-8/MRP-14 was correlated with MMP-9 in the acute phase of KD patients (r=0.503, P=0.00). MRP-8/MRP-14 was correlated with CD11bmRNA in the acute phase of KD patients (r=0.782, P=0.00). MMP-9 was correlated with CD11bmRNA in the acute phase of KD patients (r=0.540, P=0.00).6. MRP-8/-14 was correlated with white blood cell count and neutrophil percentage in the acute phase of KD patients (r=0.483, P=0.001; r=0.310, P=0.036). MRP-8/MRP-14 was not correlated with Platelet (r=0.059, P=0.697). MMP-9 was correlated with white blo-od cell count and neutrophil percentage in the acute phase of KD patients (r=0.598, P=0.00; r=0.453, P=0.02). CD11b was correlated with white blood cell count and neutrophil percentage in the acute phase of KD patients (r=0.404, P=0.005; r=0.367, P=0.012).Conclusion:1. MRP-8/MRP-14, Neutrophil adhesion molecule CD11b and MMP-9 may probably play a role in the pathogenesis of vasculitis and can be used as a reference indicator in KD.2. MRP8/MRP14, Neutrophil adhesion molecule CD11b and MMP-9 were correlated with each other in KD. they together participate in KD inflammation, especially endothelia lesion and platelet activation. And they may be involved in the formation of CAL. They can be used as one of the indicators to predict the CAL formation.3. MRP8/MRP14 and CD11bmRNA were still higher than the febrile group and the healthy control group in the subacute of KD, indicating the persistence of inflammation and endothelial microvascular injury. This suggested that anti-inflammation of anticoagulation therapy remains need in the subacute of KD.4. MRP-8/MRP14, MMP-9 and CD11b were correlated with white blood cell count and neutrophil percentage in the acute phase of KD patients.It demonstrated that they were closely related with acute inflammation activity of KD. They are closely connected the severity of inflammation.