Purpose: Exaggerated pro-inflammatory reactions during the acute phase of Kawasaki disease (KD) suggest the role of immune dysregulation in the pathogenesis of KD. We investigated the profiles of T regulatory cells and their correlation with the clinical course of KD. Methods: Peripheral blood monon...
Purpose: Exaggerated pro-inflammatory reactions during the acute phase of Kawasaki disease (KD) suggest the role of immune dysregulation in the pathogenesis of KD. We investigated the profiles of T regulatory cells and their correlation with the clinical course of KD. Methods: Peripheral blood mononuclear cells were collected from 17 KD patients during acute febrile and subacute afebrile phases. T cells expressing CD4, CD25, and Foxp3 were analyzed using flow cytometry, and the results were correlated with the clinical course of KD. Results: The percentage of circulating $CD4^+CD25^{high}Foxp3^+$ T cells among $CD4^+$ T cells was Significantly higher during the subacute afebrile phase than during the acute febrile phase ($1.10%{\pm}1.22%$ vs. $0.55%{\pm}0.53%$, P=0.049). Although levels of $CD4^+CD25^{low}Foxp3^+$ T cells and $CD4^+CD25^-Foxp3^+$ T cells were only slightly altered, the percentage of $CD4^+CD25^+Foxp3^-$ T cells among $CD4^+$ T cells was significantly lower during the subacute afebrile phase than during the acute febrile phase ($2.96%{\pm}1.95%$ vs. $5.64%{\pm}5.69%$, P=0.036). Consequently, the ratio of $CD25^{high}Foxp3^+$ T cells to $CD25^+Foxp3^-$ T cells was higher during the subacute afebrile phase than during the acute febrile phase ($0.45%{\pm}0.57%$ vs. $0.13%{\pm}0.13%$, P=0.038). Conclusion: Decreased $CD4^+CD25^{high}Foxp3^+$ T cells and/or an imbalanced ratio of $CD4^+CD25^{high}Foxp3^+$ T cells to $CD4^+CD25^+Foxp3^-$ T cells might playa role in KD development. Considering that all KD patients were treated with intravenous immunoglobulin (IVIG), recovery of $CD4^+CD25^{high}Foxp3^+$ T cells during the subacute afebrile phase could be a mechanism of IVIG.
Purpose: Exaggerated pro-inflammatory reactions during the acute phase of Kawasaki disease (KD) suggest the role of immune dysregulation in the pathogenesis of KD. We investigated the profiles of T regulatory cells and their correlation with the clinical course of KD. Methods: Peripheral blood mononuclear cells were collected from 17 KD patients during acute febrile and subacute afebrile phases. T cells expressing CD4, CD25, and Foxp3 were analyzed using flow cytometry, and the results were correlated with the clinical course of KD. Results: The percentage of circulating $CD4^+CD25^{high}Foxp3^+$ T cells among $CD4^+$ T cells was Significantly higher during the subacute afebrile phase than during the acute febrile phase ($1.10%{\pm}1.22%$ vs. $0.55%{\pm}0.53%$, P=0.049). Although levels of $CD4^+CD25^{low}Foxp3^+$ T cells and $CD4^+CD25^-Foxp3^+$ T cells were only slightly altered, the percentage of $CD4^+CD25^+Foxp3^-$ T cells among $CD4^+$ T cells was significantly lower during the subacute afebrile phase than during the acute febrile phase ($2.96%{\pm}1.95%$ vs. $5.64%{\pm}5.69%$, P=0.036). Consequently, the ratio of $CD25^{high}Foxp3^+$ T cells to $CD25^+Foxp3^-$ T cells was higher during the subacute afebrile phase than during the acute febrile phase ($0.45%{\pm}0.57%$ vs. $0.13%{\pm}0.13%$, P=0.038). Conclusion: Decreased $CD4^+CD25^{high}Foxp3^+$ T cells and/or an imbalanced ratio of $CD4^+CD25^{high}Foxp3^+$ T cells to $CD4^+CD25^+Foxp3^-$ T cells might playa role in KD development. Considering that all KD patients were treated with intravenous immunoglobulin (IVIG), recovery of $CD4^+CD25^{high}Foxp3^+$ T cells during the subacute afebrile phase could be a mechanism of IVIG.
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제안 방법
All of the subjects were treatol with IVIG, and a series of changes were expected after defervecencx. One working mechanism oflVIG is to bind to cells that seaete inflammatory cytokines and chemokines andpress the secretion!7).
In the same way, phycoerythin (PE)-antihuman Foxp3 antibody (eBioscience, San Diego, CA, USA) was administered, marked, and rinsed. The subjects were classified into four groups, i.e., a control group, a 흉roup of mononuclear cells marked by antihuman CD4 and CD25 antibodies, a group marked by die antihuman Foxp3 antibody and a group marked by both antihuman CD4 and CD25 antibodies and antihuman Foxp3 antibodies. The subjects were then analyzed by the use of flowcytometry (EACSCalibur, CellQuest software, Becton Dickinson Immunocytometry System, San Jose, CA, USA) Expression of CD25 and Foxp3 were determined in gated CD4+ T cells, and consequently each cell population was expressed as the percent of CD4+ T cells, Foxp3+ T cells, based on their CD25 expression, were divided into three populations: CD4+CD25~Foxp3+ T cells, CDfCDZegFoxpe T cells, and CD4tCD25hw, Foxp3+ T cells (Fig.
, a control group, a 흉roup of mononuclear cells marked by antihuman CD4 and CD25 antibodies, a group marked by die antihuman Foxp3 antibody and a group marked by both antihuman CD4 and CD25 antibodies and antihuman Foxp3 antibodies. The subjects were then analyzed by the use of flowcytometry (EACSCalibur, CellQuest software, Becton Dickinson Immunocytometry System, San Jose, CA, USA) Expression of CD25 and Foxp3 were determined in gated CD4+ T cells, and consequently each cell population was expressed as the percent of CD4+ T cells, Foxp3+ T cells, based on their CD25 expression, were divided into three populations: CD4+CD25~Foxp3+ T cells, CDfCDZegFoxpe T cells, and CD4tCD25hw, Foxp3+ T cells (Fig. 1).
대상 데이터
In the other nine jetients where the 시inical manifestations did not fulfill the diagnostic criteria and other diagnoses were excluded, symptoms that are frequently associated with KD and elevated inflammatory indices during the acute phase were considered to support the diagnosis of incomplete KD8, 9\ These cases of incomplete KD wae only included in this analysis if they showed a typical convalescent condition such as skin peeling. All 17 subjects were treated with immveiNius immunoglobulin (IVIG, 2 g/kg in addition to aspirin (50-80 mg/ kg/da少.Echocardiography was performed usually at 7~10 days after onset of fever and tberrafter at monthly intervals for at least 2 months.
This study was performed on 17 patients diagnosed with KD letween March and November, 2008 at Korea University Medical Center Ansan Hospital. The cases were characterized by a fever of more than 385* that continued for at least 5 days and was accompanied by at least four out of the following five symptoms: jx)lymorphous rash, extremity changes, cervical lymphadenopathe conjunctival injection, and distinctive or시 manifestations.
데이터처리
For statistical analysis, SPSS (version 12.0, SPSS Inc., Chicago, Ⅱ., USA) was used with the faired t-test. Only cases in which the P value was less than 0.
성능/효과
In conclusion, decreased CD4+CD25lughFoxp3+ T cells, increased CD4+CD25+Foxp3 T cells, and/or an imbalanced ratio of CD25 highFoxp3+ T cells to CD4+CD25+Foxp3~ T cells might be related to the immune activation that occurs during the acute phase ofKD. Reversal of these jwameters vhi사! was observed during the sufecute afebrile phase, is likely a result of the treatment with IVIG- lb define the roles of Tregs in the pathogenesis ofKD, further studies that include normal controls as well as other febrile disease controls are needed.
It is impossible to analyze the Rinction of Foxp3" cells, because it is expressed intracellularly and its identification requires the fixation and permeabilization of cells. In this study, CD4*Foxp3+ Tregs were divided into CD25 T cells, CD25 T cells, and CD25 T cells according to the degree of expression of CD25, and the numerical pattern of expression in these cells was correlated with the alinice courses ofKD. During the acute phase, the proportion of CD4*CD25Foxp3* T celk was lower than that during the subacute phase, which clinically corresponded to their suppressive regulatory function.
후속연구
ofKD. Reversal of these jwameters vhi사! was observed during the sufecute afebrile phase, is likely a result of the treatment with IVIG- lb define the roles of Tregs in the pathogenesis ofKD, further studies that include normal controls as well as other febrile disease controls are needed.
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