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성인 기관지천식 환자들에서 기도상피세포 단백에 대한 자가항체의 IgG 아형 분포
권별 ( Byul Kwon ),신지영 ( Jee Young Shin ),김정은 ( Jeong Eun Kim ),예영민 ( Young Min Ye ),서창희 ( Chang Hee Suh ),박해심 ( Hae Sim Park ),남동호 ( Dong Ho Nahm ) 대한천식알레르기학회 2005 천식 및 알레르기 Vol.25 No.4
Background: A possible involvement of autoimmune response to the against airway mucosa tissue in the pathogenesis of nonatopic asthma has been proposed by the earlier studies. Recently, a cytokeratin 18 protein has been identified as an airway epithelial cell autoantigen recognized by circulating IgG autoantibodies from patients with nonatopic asthma. Objective: In this study, we evaluated an IgG subclass distribution of circulating IgG autoantibodies to airway epithelial cell proteins in the serum samples from adult patients with bronchial asthma. Method: IgG subclass (IgG1, IgG2, IgG3, and IgG4) autoantibodies to airway epithelial cell proteins were detected in serum samples from patients with atopic asthma and patients with nonatopic asthma, and healthy controls by Western blot analysis. Result: Detection rate of IgG1 and IgG4 autoantibodies to cytokeratin 18 protein was significantly higher in patients with nonatopic asthma (3/12; 25%) compared to healthy controls (0/12; 0%) and patients with atopic asthma (0/12; 0%)(Chi-square test; P<0.05). However, there was no significant difference in the detection rate of IgG2 and IgG3 autoantibodies to cytokeratin 18 proteins among the three groups (P>0.05). Conclusion: The predominance of circulating IgG1 and IgG4 autoantibodies to cytokeratin 18 protein in patients with nonatopic asthma suggests a possibility of autoantibody-mediated complement activation and chronic activation of autoantigen-specific Th1 and Th2 cells. (Korean J Asthma Allergy Clin Immunol 2005;25:313-319)
성인 천식 환자들에서 Cytokeratin 18 단백에 대한 IgG 자가항체와 천식의 임상적 중증도 간의 연관성
신지영 ( Jee Young Shin ),권별 ( Byul Kwon ),신호수 ( Ho Su Sin ),예영민 ( Young Min Ye ),박해심 ( Hae Sim Park ),남동호 ( Dong Ho Nahm ) 대한천식알레르기학회 2006 천식 및 알레르기 Vol.26 No.3
Background: Cytokeratin 18 (CK18) protein was identified as an airway epithelial cell antigen associated with nonallergic asthma. Objective: We evaluated an association between IgG autoantibodies to CK18 protein and clinical severity of asthma in this study. Method: Severe asthma was defined as when patients had experienced at least one severe asthmatic exacerbation requiring an emergency room visit or admission in the last year despite continuous typical therapies. Moderate asthma was defined as when patients had been controlled by typical therapies without severe asthmatic exacerbation in the last year. Mild asthma was defined as when patients experienced intermittent asthmatic symptoms and did not need continuous anti-asthmatic treatments in the last year. IgG autoantibodies to CK18 protein were detected in serum samples by immunoblot analysis Result: IgG autoantibodies to CK18 protein were detected in 48 of 161 asthmatic patients (29.8%) and 5 of 58 healthy controls (8.6%) (P=0.002). IgG autoantibodies to CK18 protein were detected in 1 of 20 patients with mild asthma (5.0%), 22 of 63 patients with moderate asthma (34.9%), and 25 of 78 patients with severe asthma (32.1%)(P<0.001). Conclusion: These findings suggest that IgG autoantibodies to CK18 protein could be a biological marker for moderate-to-severe asthma requiring continuous medical treatment. (Korean J Asthma Allergy Clin Immunol 2006;26:219-224)
기관지천식과 관련된 기도상피세포 자가항원의 단백체 분석: 세포배양 분획을 활용한 표적단백질의 규명 방법
이혜아 ( Hye Ah Lee ),이연정 ( Yeon Jeong Lee ),권별 ( Byul Kwon ),최길순 ( Gil Soon Choi ),박한정 ( Han Jung Park ),예영민 ( Young Min Ye ),박해심 ( Hae Sim Park ),강엽 ( Yup Kang ),남동호 ( Dong Ho Nahm ) 대한천식알레르기학회 2008 천식 및 알레르기 Vol.28 No.3
Background: Involvement of the autoimmune mechanism has been suggested for the pathogenesis of bronchial asthma and several autoantigens which are associated with bronchial asthma have been identified. Objective: To identify novel asthma-associated autoantigens by proteomic analysis of proteins which are extracted by the cultured cell fractionation method according to the physical affinity of airway epithelial cells(A549) to the culture matrix. Method: Autoantigens were screened with serum samples from patients with severe asthma and the target autoantigens were identified by mass spectrometry. Result: Cultured A549 cells were differentially fractionated into easily detachable floating cell fraction and firmly attached cell fraction. Easily detachable cell fraction containing senescent cell and necrotic cell debris had many detectable asthma-related autoantigens when screened by immunoblot analysis using IgG antibodies from patients with severe asthma. In mass spectrometry analysis of 95-kDa autoantigen, ailpha-actin 4 was identified as a new airway epithelial autoantigen which was recognized by IgG autoantibody from a patient with severe asthma. This was reconfirmed by using specific antibody. Conclusion: Proteomic analysis of the airway epithelial cells using the differential fractionation method according to the physical characteristics of cultured airway epithelial cells may be a novel method for the identification of additional asthma- related autoantigens. (Korean J Asthma Allergy Clin Immunol 2008;28:192-198)
중증 천식 및 만성폐쇄성폐질환 환자에서 IgG 자가항체가 인지하는 기도상피세포 자가항원 단백질 분석
이혜아 ( Hye Ah Lee ),박주헌 ( Joo Hun Park ),권별 ( Byul Kwon ),최길순 ( Gil Soon Choi ),예영민 ( Young Min Ye ),박해심 ( Hae Sim Park ),남동호 ( Dong Ho Nahm ) 대한천식알레르기학회 2009 천식 및 알레르기 Vol.29 No.4
Background: The presence of circulating autoantibodies to airway epithelial cells has been reported in patients with asthma and chronic obstructive pulmonary disease (COPD). Objective: To evaluate the possibility of a common autoantigen associated with both asthma and COPD, we analyzed airway epithelial cell autoantigens recognized by circulating IgG autoantibodies from patients with severe asthma and COPD. Method: IgG autoantibodies to human airway epithelial cells (A549) were examined in serum samples from patients with severe asthma and COPD by immunoblot analysis. Result: A 54-kDa airway epithelial autoantigen was commonly recognized by circulating IgG antibodies from patients with severe asthma and COPD. The 54-kDa autoantigen was identified as cytokeratin 8 protein by mass spectrometry. IgG autoantibodies to recombinant human cytokeratin 8 protein were detected in serum samples from 5 (31.3%) of the 16 patients with severe asthma, 4 (26.6%) of 15 patients with COPD, 1 (7.7%) of 13 patients with mild-to-moderate asthma, and 1 (7.7%) of 13 healthy controls (P=0.056). Conclusion: In this study, we identified cytokeratin 8 as an airway epithelial autoantigen associated with both severe asthma and COPD. Further studies are needed to determine the role of this autoantigen in the pathogenesis of severe asthma and COPD. (Korean J Asthma Allergy Clin Immunol 2009;29:249-255)