The role of activation of toll-like receptors in immunological pathogenesis of Kawasaki disease / 中华儿科杂志

<p><b>OBJECTIVE</b>A great deal of clinical evidence and epidemiologic data suggest that Kawasaki disease (KD) is correlated with an acute regulating imbalance of immunology. Lots of evidences in the past suggested that nuclear transcription factor-kappaB and preinflammation factors were up-regulated significantly in patients with KD. But the causative factors are still unknown. Toll-like receptors (TLRs) is a type I trans-membrane protein which could recognize ligands of pathogen microbes, activate the nuclear transcription factor-kappaB and promote gene transcription of pre-inflammation factors and co-stimulatory molecules on cell surface. Aberrant activation of signal pathway of TLRs could interfere with autoimmune tolerance and cause autoimmune diseases. The study was designed to investigate the role of signal transduction of TLRs on immunological pathogenesis of KD.</p><p><b>METHODS</b>Sixteen children with KD and 16 age-matched health children were studied. Reverse-transcription PCR (RT-PCR) and real-time PCR were used to evaluate the levels of TLRs 1 - 10, MD-2, MyD88, IL-1beta, IL-6 and IL-8 mRNA expressions in peripheral blood mononuclear cells, and expressions of TLRs 2, 4 and co-stimulatory molecules such as CD80 and CD86 in monocyte/macrophage were analyzed by flow cytometry.</p><p><b>RESULTS</b>(1) Compared with control group, the protein and mRNA levels of TLR4 in KD group were up-regulated significantly [(Real-time PCR: 325.22 +/- 50.34 vs. 2.20 +/- 0.23, P < 0.01); (flow cytometry: 15.96% +/- 5.94% vs. 3.21% +/- 0.62%, P < 0.01)], the difference being not significant as to other TLRs. (2) Transcriptional levels of MD-2 and Myd88 were significantly up-regulated in acute phase of KD (P < 0.01), and down-regulated after the treatment with intravenous gamma globulin therapy. (3) Expressions of co-stimulatory molecules and cytokines in monocyte/macrophage during acute phase of KD were higher than those of control group (P < 0.01).</p><p><b>CONCLUSION</b>Expressions of TLRs 4, MD-2 and Myd88 were up-regulated during acute phase in KD, suggesting that aberrant activation of TLRs 4 might be one of the initiating factors of immune aberrance in KD.</p>

Distribution of Specific Immunoglobulin E and Total Immunoglobulin E in Children with Respiratory Allergic Disease / 实用儿科临床杂志

Objective To study the distribution of sepecific immunoglobulin E(SIgE) and its relationship with the total immunoglo-(bulin) E(TIgE) in children with respiratory allergic disease.Methods Serum SIgE was measured in 209 children with asthma,allergic rhinitis,cough variant asthma and asthmatic bronchitis by Pharmacia UniCAP100E system.The SIgE included the SIgE antibodies to fx5E(egg albumen,milk,fish,wheat,peanut,soybean),hx2(house dust,dermatophagoides culinae,dermatophagoides pteronyssinus,cockroach),ex1(scurf of cat,horse,cow and dog),mx1(penicillium notatum,helminthosporium halodes,aspergillums furngatits,alternaria allcrnata,),f23(crab),f14(shrimp),w14(amaranthaceae),T21(cajeput) and i8(moth).Serum TIgE was also detected in 132 patients.Results 1.The positive detection rate of SIgE in patients aged from 3 to 14 years were 72.81% which were higher than that of aged from 40 days to 3 years old(57.89%).2.The SIgE detection rate of fx5E,hx2 and ex1 were 81.8%,32.73% and 16.36% respectively in patients aged from 40 days to 3 years old;but that of hx2,fx5E,i8,w14,f24 and ex1 were 78.31%,48.19%,24.10%,24.10%,15.66% and 15.66% respectively in patients aged from 3 to 14 years.3.The positive detection rate of SIgE was related with that of TIgE.The detection rate of combined SIgE and the TIgE was 83.33%.Conclusions 1.The lower detection rate of SIgE in patients aged from 40 days to 3 years may be due to the wheezing in infants partially induced by the acute infection and congenital airway disease.2.The most common allergens in children aged from 40 days to 3 years were fx5E,hx2 and ex1.But that of patients aged from 3 to 14 years were hx2,fx5E,i8,w14,f24 and ex1.3.The combined detection of the SIgE and the TIgE may increase the positive rate and diagnose the patients with respiratory allergic disease effectively.

The role of negative-regulatory factors of toll-like receptors signal pathways in the immunological pathogenesis of Kawasaki disease / 中华风湿病学杂志

Objective To investigate the role of negative-regulatory factors of toll-like receptors (TLRs)signal pathways in immunological pathogenesis of Kawasaki disease(KD).Methods Thirty-two chil- dren with Kawasaki disease and 16 age-matched healthy children were studied.Reverse-transcription PCR (RT-PCR)and real-time PCR were used to evaluate the mRNA expression levels of toll-like receptor 4(TLR4), MD-2,MyD88,IRAK-4,TRAF6,T1/ST2,IRAK-M,Triad 3A,and proinflammatory factors such as IL-1?, IL-6,IL-8 and TNF-?,in peripheral blood monocytes/macrophages(MC).The expression of TLR4 protein in MC was analyzed by flow cytometry.Results①Compared with the control group,the mRNA levels of TLR4, MD-2,MyD88,IRAK-4 and TRAF6 in KD group were up-regulated significantly(P＜0.01),and the expression level of TLR4 protein was also found to be up-regulated in KD group during acute phase.It was detected that expression levels of TLR4 protein in KD with coronary artery lesion(KD-CAL~+)was significantly higher than that of KD without coronary artery lesion(KD-CAL-)[flow cytometry:(6.5?1.7)% vs(11.9_+2.4)%,P＜0.01].②The expression level of negative-regulatory factors such as IRAK-M and Triad3A were significantly up-regulat- ed in acute phase of Kawasaki disease,while the mRNA levels of IRAK-M and Triad3A in KD-CAL~+ group was found to be significantly lower than those of KD-CAL~- group(P＜0.01).No difference of T1/ST2 mRNA expres sion level was detected among all groups(P＞0.05).③The expressions of proinflammatory eytokines such as IL-1?, IL-6,IL-8 and TNF-?in monoeytes/macrophages during acute phase of Kawasaki disease were higher than those of the control group(P＜0.01),and expression of proinflammatory cytokines in KD-CAL~+ group was significantly higher than that of KD-CAL~- group.Conclusion Relative insufficient expression of negative-regulatory factors, such as IRAK-M and Triad3A,maybe correlate with immunological pathogenesis of Kawasaki disease.