2.Decreased CD5+ B cells during the acute phase of Kawasaki disease.
Hee Soo KIM ; Geun Woong NOH ; Dong Soo KIM ; Ki Young LEE ; Hee Sun LEE ; Hong Kyu LEE ; Soon Il LEE
Yonsei Medical Journal 1996;37(1):52-58
We investigated the changes of CD5+ B cells in the peripheral blood of 20 Kawasaki disease (KD) patients. The percentage of CD5+ B cells in the total lymphocytes and in the total B cells significantly decreased during the acute phase of KD(p< 0.01), compared to that in the age-matched normal control subjects. After intravenous immunoglobulin(IVIG) treatment, the percentage of CD5+ B cells increased, but was still lower than that in the normal controls(p< 0.01). During the convalescent phase of the disease, the percentage of CD5+ B cells was restored to the normal levels. The levels of CD5+ B cell percentage in the total B cells of the patients with acute febrile disease showed similar levels to age-matched normal controls. The decreased CD5+ B cells in the patients with KD provides an additional abnormal immunological finding during the acute phase of the disease.
Acute Disease
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Antigens, CD5/*analysis
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B-Lymphocytes/*immunology
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Child
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Child Preschool
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Female
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Human
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Infant
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Male
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Mucocutaneous Lymph Node Syndrome/*immunology/physiopathology
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Reference Values
3.Production and Expression of Gro-alpha and RANTES by Peripheral Blood Mononuclear Cells Isolated from Patients with Kawasaki Disease and Measles.
Hee Sun KIM ; Won Duk KIM ; Young Hwan LEE
Journal of Korean Medical Science 2003;18(3):381-386
We investigated whether the production and gene expression of Gro-alpha and RANTES in Kawasaki disease differ in measles. Forty-two samples from 14 patients in different clinical stages of Kawasaki disease, eight samples from 8 patients in the acute stage of measles and seven samples from 7 healthy children were collected. The present study was performed using ELISA and RT-PCR for the productions and gene expression of the chemokines. The production of Gro-alpha was markedly elevated during the acute stage of measles compared with Kawasaki disease. Moreover, the expression of Gro-alpha was increased in every case of measles, but not in Kawasaki disease. The production of RANTES was elevated in the acute stage of both diseases when compared to the healthy control. However, the plasma RANTES level did not change significantly according to the clinical stages of Kawasaki disease. A correlation between the production and gene expression of RANTES and Gro-alpha was not found in Kawasaki disease. These results suggest that Kawasaki disease differs from measles with regard to Gro-alpha production and expression, but not RANTES. Gro-alpha might play an important role in the acute stage of measles, however not in Kawasaki disease. Further studies are needed to clarify the efficacy of Gro-alpha as a marker in measles.
Biological Markers
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Chemokines/blood/*genetics
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Chemotactic Factors/blood/*genetics
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Child
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Child, Preschool
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Comparative Study
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Female
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Gene Expression/immunology
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Human
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Infant
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Intercellular Signaling Peptides and Proteins/blood/*genetics
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Leukocytes, Mononuclear/*physiology
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Male
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Measles/*immunology/physiopathology
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Mucocutaneous Lymph Node Syndrome/*immunology/physiopathology
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RANTES/blood/*genetics
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RNA, Messenger/analysis
4.Changes and significance for regulatory factors for signal pathways of Toll-like receptors in immunological pathogenesis of Kawasaki disease.
Guo-bing WANG ; Cheng-rong LI ; Ying ZU ; Wei-guo YANG
Chinese Journal of Pediatrics 2008;46(1):49-54
OBJECTIVEMany clinical evidences and epidemiologic data in the past suggested that Kawasaki disease (KD) is correlated with an acute immune dysfunction caused by infection. In our preliminary study, Toll-like receptor 4 signal pathway, which could activate nuclear transcription factor-kappaB and induce excessive product of proinflammatory cytokines, chemokines and co-stimulatory molecules, was observed to be significantly activated during acute phase of Kawasaki disease. But the causative factors and regulatory mechanism are still unknown. In this study, the authors further investigated the changes and significances of regulatory factors for signal pathway of Toll-like receptors (TLRs) in immunological pathogenesis of Kawasaki disease.
METHODSForty-eight children with KD, sixteen children with infectious disease (ID) and sixteen age-matched healthy children were studied. Reverse-transcription PCR (RT-PCR) and real-time PCR were used to evaluate the expression levels of regulatory and effective factors in toll-like receptor 4 (TLR4) signal pathways and proinflammatory factors in peripheral blood monocyte/macrophage (MC). The expression of TLR4 protein in MC was analyzed by flow cytometry.
RESULTS(1) Expression levels of TLR4, MD-2, MyD88, IRAK-4, TRAF6, TAK1, TAB1 and TAB2 mRNA in KD group were elevated significantly during acute phase (P < 0.05). (2) Transcription levels of regulatory factors PRAT4B and STAP2 in patients with KD or ID were found to be higher than those in the healthy volunteers (P < 0.05), but no significant differences in these parameters were detected between KD patients and ID patients (P > 0.05). Transcription levels of regulatory factors such as FLN29, RP105 and MD-1 were up-regulated to some extents and expression level of DAP12 mRNA in KD patients were found to be lower than that in normal controls (P < 0.05), while all of the four regulatory factors were found to be lower than those in ID patients (P < 0.05). Expressions of proinflammatory cytokines such as L-1beta, IL-6 and TNF-alpha in KD patients were significantly higher than those in ID patients (P < 0.05). (3) Stimulation with lipopolysaccharide (LPS) elevated remarkably the expressions of regulatory factors PRAT4B and STAP2 in KD patients or healthy volunteers (P < 0.05). All of the four negative-regulatory factors were found to be significantly up-regulated after stimulation with LPS in controls (P < 0.05). No responses to LPS were observed in expression of FLN29, RP105 and MD-1 mRNA in KD patients (P > 0.05), except for increased transcription of DAP12. (4) The levels of PRAT4B and STAP2 mRNA in KD patients with coronary artery lesion (KD-CAL(+)) were detected to be higher than those in KD patients without coronary artery lesion (KD-CAL(-)) during acute phase (P < 0.05), while those of FLN29, RP105 and MD-1 in KD-CAL(+) group were lower than that in the latter (P < 0.05). No significant difference in DAP12 mRNA expression level was detected between the two groups (P > 0.05). Expressions of proinflammatory cytokines and TLR4 protein on surface of CD14-positive cells in KD-CAL(+) group were found to be higher than those in KD-CAL(-) group [(11.9 +/- 2.4)% vs. (6.5 +/- 1.7)%, P < 0.05].
CONCLUSIONDisturbance of negative-regulatory factors may be one of the factors causing aberrant immunological function in KD.
Child ; Coronary Vessels ; drug effects ; physiology ; Cytokines ; metabolism ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Lipopolysaccharides ; toxicity ; Macrophages ; drug effects ; pathology ; Mucocutaneous Lymph Node Syndrome ; immunology ; metabolism ; physiopathology ; RNA, Messenger ; blood ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; physiology ; Toll-Like Receptors ; immunology ; metabolism ; Tumor Necrosis Factor-alpha ; pharmacology ; Up-Regulation