27 rats were immunized with synthetic ANT peptide. Antibody titers in sera and heartfunctions were measured at day 14, 28 and 42 arter the latest immunization. The results showed thatIn the 27 rats immuuized with the ...27 rats were immunized with synthetic ANT peptide. Antibody titers in sera and heartfunctions were measured at day 14, 28 and 42 arter the latest immunization. The results showed thatIn the 27 rats immuuized with the ANT Peptide, 63% (17/27) showed marked increasing or specificanti-ANT-Peptide antibody titers in sera. The highest positive rate of antibodies in sera is on the 28th day after the latest immunization. Remarkabie impairment of cardiac functions was observed simultaneously. Correlaled analysis indicates that the degree of the declined cardiac function relatedclosely with the levels of antibody titers. It is indicated that anti-ANT-antibody is a specific,Pathogenic autoantibody to heart. The synthetic ANT peptide we select could replace the native ANTprotein in further studies of the pathogenesis of antiboies against ANT.展开更多
To probe the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM) 77 patients with DCM, HLA DRB1 gene polymorphism were analyzed by using t he polymerase chain reaction /sequence specific primer ...To probe the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM) 77 patients with DCM, HLA DRB1 gene polymorphism were analyzed by using t he polymerase chain reaction /sequence specific primer (PCR/SSP) technique and a utoantibody against myocardial mitochondria ADP/ATP carrier were examined by usi ng the Immunoblot analysis. The frequency of HLA DRB1*0901 allele was significa ntly higher in DCM patients in which autoantibody against ADP/ATP carrier of myo cardial mitochondria is positive in contrast with those in which the autoantibod y is negative (25.46 % vs 3.45 %, P <0.05), the relative risk (RR) being 9.5 6. The other frequencies of HLA-DRB1 alleles have no significant difference in the antibody positive group and negati ve group. It is possible that a subset of DCM patients may exist in which autoi mmunity is associated with genetic factors.展开更多
The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice t...The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice （6–8 weeks old） were randomized into 3 groups： dilated cardiomyopathy （DCM） group, DCM-tolerance （Tol） group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were moni- tored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group （P〈0.01）. On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group （P〈0.01）, and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.展开更多
文摘27 rats were immunized with synthetic ANT peptide. Antibody titers in sera and heartfunctions were measured at day 14, 28 and 42 arter the latest immunization. The results showed thatIn the 27 rats immuuized with the ANT Peptide, 63% (17/27) showed marked increasing or specificanti-ANT-Peptide antibody titers in sera. The highest positive rate of antibodies in sera is on the 28th day after the latest immunization. Remarkabie impairment of cardiac functions was observed simultaneously. Correlaled analysis indicates that the degree of the declined cardiac function relatedclosely with the levels of antibody titers. It is indicated that anti-ANT-antibody is a specific,Pathogenic autoantibody to heart. The synthetic ANT peptide we select could replace the native ANTprotein in further studies of the pathogenesis of antiboies against ANT.
基金the Chinese Ministry ofPublic Health(No96-2 -1 0 5 )
文摘To probe the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM) 77 patients with DCM, HLA DRB1 gene polymorphism were analyzed by using t he polymerase chain reaction /sequence specific primer (PCR/SSP) technique and a utoantibody against myocardial mitochondria ADP/ATP carrier were examined by usi ng the Immunoblot analysis. The frequency of HLA DRB1*0901 allele was significa ntly higher in DCM patients in which autoantibody against ADP/ATP carrier of myo cardial mitochondria is positive in contrast with those in which the autoantibod y is negative (25.46 % vs 3.45 %, P <0.05), the relative risk (RR) being 9.5 6. The other frequencies of HLA-DRB1 alleles have no significant difference in the antibody positive group and negati ve group. It is possible that a subset of DCM patients may exist in which autoi mmunity is associated with genetic factors.
基金the National Natural Science Foundation of China (No. 30000070)
文摘The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice （6–8 weeks old） were randomized into 3 groups： dilated cardiomyopathy （DCM） group, DCM-tolerance （Tol） group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were moni- tored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group （P〈0.01）. On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group （P〈0.01）, and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.
