[Effect of IL-17A on levels of antiheart autoantibodies in mice with viral myocarditis].

OBJECTIVE: To explore the effect of interleukin-17A (IL-17A) on the serum level of antiheart autoantibodies in mice with viral myocarditis. METHODS: Male wild-type (WT) and IL-17A-deficient (IL-17A(-/-)) BALB/c mice were intraperitoneally injected with Coxsackie virus B3 (CVB3) for establishing VMC models (VMC-WT group and VMC-IL-17A(-/-) group). Meanwhile, a control group (WT group) of WT mice were established by i.p. administration of phosphate buffered saline (PBS). Paraffin sections of cardiac tissues were made 14 days after CVB3 injection. Myocardial histopathologic changes were evaluated by HE staining. The levels of anti-adenine nucleotide translocator (ANT) autoantibody, anti-ß-myosin heavy chain (ß-MHC) autoantibody and anti-cardiac L-type calcium channel (CACH2) autoantibody in sera were measured by ELISA. RESULTS: Compared with WT group, the levels of anti-ANT-autoantibody and anti-ß-MHC-autoantibody significantly increased in VMC-WT group (P<0.01, P<0.05), while the concentration of anti-CACH2-autoantibody showed no significant difference between WT and VMC-WT groups (P>0.05). Compared with VMC-WT group, the level of anti-ANT-autoantibody was reduced in VMC-IL-17A(-/-) group (P<0.05), while the levels of anti-ß-MHC-autoantibody and anti-CACH2-autoantibody showed no significant difference between them (P>0.05). CONCLUSION: IL-17A contributed to the secretion of anti-ANT-autoantibody of VMC mice, but had no effect on the secretion of anti-ß-MHC-autoantibody and anti-CACH2-autoantibody in VMC mice.

Analysis of specific Th1/Th2 helper cell responses and IgG subtype antibodies in anti-CD4 monoclonal antibody treated mice with autoimmune cardiomyopathy.

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-gamma and IL-4 of Th cells were monitored with flow cytometry, and splenic T cell cytokines IFN-gamma, 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.

Leishmania mexicana amazonensis: plasma membrane adenine nucleotide translocator and chemotaxis.

Leishmania cannot synthesize purines de novo and rely on their host to furnish these compounds. To accomplish this, they possess multiple purine nucleoside and nucleobase transporters. Subcellular fractionation, immunohistochemical localization with anti-adenine nucleotide translocator (ANT) antibodies and surface biotinylation show that the mitochondrial ANT is also present in the plasma membrane of both promastigotes and amastigotes. Leishmania, however, do not appear to rely on this transporter to supplement their purine or energy requirements via preformed ATP from its host. Rather, Leishmania appear to use the plasma membrane ANT as part of a chemotaxis response. ATP is a chemorepellant for Leishmania and cells treated with atractyloside, an inhibitor of ANT, no longer exhibit negative chemotaxis for this compound.

Analysis of IgG subclass antibodies and expression of T-Cell receptor signaling molecules in anti-CD4 monoclonal antibody treated mice with autoimmune cardiomyopathy.

T-cell immune abnormality in patients of dilated cardiomyopathy has been intensively studied over the past 10 years. In this study, we aim to focus on the molecular mechanism of T-cells in autoimmune cardiomyopathy mouse model by detecting the expression of three T-cell signaling molecules. Balb/C mice (n = 12) were immunized with the peptides derived from human ADP/ATP carrier on the 1st, 14th, 28th, 49th and 79th days, and half of them were also injected with anti-L3T4 McAb on the - 1st, 0 and 1st days. The sham-immunized mice were taken as the controls (n = 6). The main result shows that the antibody response of IgG subclasses such as IgG1, IgG2b and IgG3 were definitely blocked except IgG2a in CD4+ cell-depleted Balb/C mice. In addition, the average mRNA expression of p56lck, p59fyn and zap-70 were all found to be dramatically higher in the mice immunized with only ADP/ATP carrier peptides than in the control-group. At meantime, reduced levels of the protein kinases p56lck, p59fyn and zap-70 were clearly observed in anti-CD4 McAb immunized group compared with DCM group. We propose that the proliferation of T-cells was significantly inhibited in anti-CD4 treated mice and CD4+ T-cells may play a critical role in ADP/ATP carrier caused mouse DCM.

Infectious tolerance to ADP/ATP carrier peptides induced by anti-L3T4 monoclonal antibody in dilated cardiomyopathy mice.

CD4 T cells are suspected to play an important role in the pathogenesis of dilated cardiomyopathy (DCM). This study sought to evaluate whether anti-L3T4 monoclonal antibody (McAb) could induce the infectious tolerance to the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier peptides to protect mice from DCM. BALB/c mice (n = 16) were immunized with the peptides derived from human ADP/ATP carrier on the 1st, 14th, 28th, 49th, and 79th days, and some of them (n = 6) were also injected with anti-L3T4 McAb on the -1st, 0, and 1st days. On the 180th day, the splenocytes (SC) from the McAb-treated group were transferred into the syngeneic recipients (n = 6) who were also immunized with the peptides in the same manner. The sham-immunized mice were taken as the controls (n = 10). Results showed that the serum antibody against the ADP/ATP carrier examined with ELISA was positive in all mice only immunized with the peptides (DCM group), while negative in the McAb-treated, the SC-transferred, and the Control groups. The mRNA expression of IFN-gamma, IL-2, and IL-4, especially IL-4 in T cells investigated using real-time quantitative PCR and the percentages of T helper 1 (Th1) and Th2 subsets, especially Th2 subset detected with Flow Cytometry were all increased in DCM group, accompanied by the cardiac histopathological changes like those in DCM. Such findings were not seen in the other three groups. It concluded that anti-L3T4 McAb could inhibit the occurrence of DCM induced by the ADP/ATP carrier peptides in mice, and this immune tolerance could be transferred to the syngeneic recipients.

Focused proteomics: towards a high throughput monoclonal antibody-based resolution of proteins for diagnosis of mitochondrial diseases.

The availability of monoclonal antibodies (mAbs) against the proteins of the oxidative phosphorylation chain (OXPHOS) and other mitochondrial components facilitates the analysis and ultimately the diagnosis of mitochondrially related diseases. mAbs against each of the five complexes and pyruvate dehydrogenase (PDH) are the basis of a rapid and simple immunocytochemical approach [Hanson, B.J., Capaldi, R.A., Marusich, M.F. and Sherwood, S.W., J. Histochem. Cytochem. 50 (2002) 1281-1288]. This approach can be used to detect if complexes have altered assembly in mitochondrial disease due to mutations in nuclear encoded genes, such as in Leigh's disease, or in mitochondrially encoded genes, e.g., MELAS. Other mAbs have recently been obtained that can immunocapture each of the five OXPHOS complexes, PDH and the adenine nucleotide translocase (ANT) from very small amounts of tissue such as that obtained from cell culture or needle biopsies from patients. When adapted to a 96-well plate format, these mAbs allow measurement of the specific activity of each of the mitochondrial components individually and analysis of their subunit composition and state of posttranslational modification. The immunocapture protocol should be useful not only in the analysis of genetic mitochondrial diseases but also in evaluating and ultimately diagnosing late-onset mitochondrial disorders including Parkinson's disease, Alzheimer's disease, and late-onset diabetes, which are thought to result from accumulated oxidative damage to mitochondrial proteins such as the OXPHOS chain.

Assessment of membrane-bound mammal mitochondrial adenine nucleotide translocase topography by experimental antibodies.

To gain insight into the immunogenicity of mitochondrial adenine nucleotide translocase (ANT), we raised antibodies against purified bovine heart ANT by induction of ascitic fluid in male Balb/c mice. We identified the antigenic determinants detected by these antibodies by (1) immunodetection of GST-ANT fusion proteins and selected partial constructs of ANT, (2) immunodetection of chemically synthesized overlapping peptides on solid support, and (3) back-titration ELISA. Results revealed a short epitope spreading of the antibodies, resulting in a small number of antigenic determinants. Thus, each antibody detects one or two major epitopes located in the putative hydrophilic loops M2 and M3. No evidence for the antigenicity of the first 133 amino acids of ANT was obtained. These well-characterized antibodies were used to study the topography of the membrane-bound ANT by back-titration ELISA with mitochondrial membranes. We demonstrated that amino acids 145-150 and 230-237 are fully accessible to the antibodies in native ANT, whereas regions 133-140 and 244-251 are not. Furthermore, we used mitochondria devoid of the outer membrane (mitoplasts) and inside-out submitochondrial particles (SMP) to establish the matrix or cytosolic orientation of loops M2 and M3. The results clearly show that these loops have a matrix orientation and thus support the six transmembrane segment model of ANT topography in the inner mitochondrial membrane.

Choline head groups stabilize the matrix loop regions of the ATP/ADP carrier ScAAC2.

ATP/ADP carriers (AACs) are essential to the cell as they exchange ATP produced in mitochondria for cytosolic ADP. Monoclonal antibodies against the isoform 2 of Saccharomyces cerevisiae AAC (ScAAC2) were used to probe the accessibility of the matrix loops 1 and 3 depending on the environment of the carrier. In mitochondrial membranes ScAAC2 was not recognized, whereas in dodecylmaltoside the antibodies bound to the carrier, suggesting that the epitopes are hidden in the native environment. Exposure of the epitopes by detergents was reversed by reconstitution of the carrier in phospholipids or by exchanging with detergents having a choline or a trimethylammonium head group. Circular dichroism spectroscopy on peptides representing the C-terminal regions of all three matrix loops showed that only phosphocholine detergents induced a structural reorganization. Since in addition phosphatidylcholine was found to be tightly associated with the purified carrier, the matrix loop regions are likely to be associated to the membrane by phosphatidylcholine.

Epitope mapping of mitochondrial adenine nucleotide translocase-1 in idiopathic dilated cardiomyopathy.

Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST-ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty-five patients with IDCM, 17 patients with ischemic left ventricle dysfunction (LVD) and 20 controls were analyzed for circulating antibodies against ANT (AAb-ANT). Sixteen of the 45 (36%) IDCM patients showed AAb-ANT above controls. In immunoblots, AAb-ANT detected purified bovine heart ANT and GST-ANT1 and GST-ANT2 isoforms and, less frequently, the GST-ANT3 isoform. A construct lacking the last 146 amino acids did not react with AAb-ANT, indicating that the main epitopes are in the C-terminal 146 amino acids. Immunodetection of decapeptides covering this region shows that AAb-ANT detects at least three epitopes, demonstrating that ANT is the primary target of AAb-ANT. The most significant epitopes belong to the M2 and M3 hydrophilic loops of ANT suggesting that apart from being essential for its activity, these loops are highly immunogenic.

Possible association of HLA-DRB1 gene with the autoantibody against myocardial mitochondria ADP/ATP carrier in dilated cardiomyopathy.

To probe the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM) 77 patients with DCM, HLA-DRB1 gene polymorphism were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique and autoantibody against myocardial mitochondria ADP/ATP carrier were examined by using the Immunoblot analysis. The frequency of HLA-DRB1*0901 allele was significantly higher in DCM patients in which autoantibody against ADP/ATP carrier of myocardial mitochondria is positive in contrast with those in which the autoantibody is negative (25.46% vs 3.45%, P < 0.05), the relative risk (RR) being 9.56. The other frequencies of HLA-DRB1 alleles have no significant difference in the antibody positive group and negative group. It is possible that a subset of DCM patients may exist in which autoimmunity is associated with genetic factors.

Adenine nucleotide translocator isoforms 1 and 2 are differently distributed in the mitochondrial inner membrane and have distinct affinities to cyclophilin D.

Different isoforms of the adenine nucleotide translocase (ANT) are expressed in a tissue-specific manner. It was assumed that ANT-1 and ANT-2 co-exist in every single mitochondrion and might be differently distributed within the membrane structures that constitute the peripheral inner membrane or the crista membrane. To discriminate between ANT originating from peripheral or from cristal inner membranes we made use of the fact that complexes between porin, the outer-membrane pore protein, and the ANT can be generated. Such complexes between porin and the ANT in the peripheral inner membrane were induced in rat heart mitochondria and isolated from rat brain and kidney. Using ANT-isotype-specific antibodies and sequence analysis of the N-terminal end, it was discovered that the peripheral inner membrane contained ANT-1 and ANT-2, whereas the cristal membrane contained exclusively ANT-2. Cyclophilin was co-purified with the porin-ANT complexes, whereas it was absent in the crista-derived ANT. This suggested that ANT-1 might have a higher affinity for cyclophilin. This specific intra-mitochondrial distribution of the two ANT isotypes and cyclophilin D suggests specific functions of the peripheral and crista-forming parts of the inner membrane and the two ANT isotypes therein.

Impairment of myocardial calcium homeostasis by antibodies against the adenine nucleotide translocator.

The adenine nucleotide translocator (ANT) is an autoantigen in myocarditis and dilated cardiomyopathy. Carrier-specific antibodies impair myocardial energy metabolism and heart function. They cross-react with a myolemmal calcium channel and alter calcium fluxes in isolated myocytes. To test whether antibodies against the ANT can alter calcium homeostasis in intact hearts, guinea pigs were immunized with the carrier protein and their isolated hearts loaded with the intracellular calcium indicator INDO-1. The diastolic and systolic ratios of fluorescence signals at 410 nm and 510 nm (emission wavelengths of the calcium-bound and calcium-free indicator), 'd-s410/510', were measured by excitation at 364 nm. This index of the transient calcium concentration associated with the contraction cycle correlated with the external heart work (EHW) in non-immunized controls. EHW of immunized animals was lower (76 +/- 62 vs 153 +/- 47 mJ/g/min in controls, p < 0.005) and the amplitude of d-s410/510 was elevated (27.6 +/- 4.1% of the average ratio of the whole heart cycle vs 21.7 +/- 1.2% in controls, p < 0.005) and essentially independent of EHW. Isoproterenol stimulation increased EHW in all hearts but d-s410/510 was hightened in control hearts, only. Thus, a disorder between cytosolic calcium transients and work was recorded in hearts from guinea pigs immunized with the ANT. It may contribute to an immunopathic mechanism of heart failure subsequent to myocarditis.

Disturbance of myocardial energy metabolism in experimental virus myocarditis by antibodies against the adenine nucleotide translocator.

OBJECTIVE: The adenine nucleotide translocator (ANT) of the inner mitochondrial membrane is an autoantigen in myocarditis and in dilated cardiomyopathy. Clinical and experimental studies showed that specific autoantibodies inhibit the transmembrane nucleotide transport. In isolated hearts of guinea pigs immunized with the ANT, energy metabolism is disturbed. This metabolic disorder is related to functionally active specific antibodies and to a reduced heart function. This study tests whether similar immunological, metabolical and functional responses also occur in experimental virus myocarditis. METHODS AND RESULTS: Experimental virus myocarditis was induced in A.SW/SnJ-mice by Coxsackie B3 virus infection. Specific antibodies against the ANT were detected by Western Blot in 14 out of 19 infected animals. In the isolated perfused hearts of five of these 14 mice cytosolic and mitochondrial ATP/ADP-ratios, determined by nonaqueous fractionation, were significantly altered, signalling a reduced ANT function [cytosolic ATP/ADP: 59 +/- 18 vs. 136 +/- 20 (controls), mitochondrial ATP/ADP: 4.2 +/- 1.0 vs. 1.1 +/- 0.3], all P < 0.05. Also, left ventricular pressure [43 +/- 9 vs. 78 +/- 6 mmHg (noninfected controls)], rate-pressure product (15.8 +/- 3.2 vs. 30.5 +/- 3.0 mmHg/min/1000), dp/dt (2410 +/- 222 vs. 3250 +/- 118 mmHg/s), and oxygen consumption (4.7 +/- 0.9 vs. 7.3 +/- 0.7 mumol/g/min), all P < 0.05, were lowered. CONCLUSION: The data support the hypothesis that a virus infection alters cardiac energy metabolism and function by an antibody-mediated modulation of the function of the ANT.

Direct demonstration of a specific interaction between cyclophilin-D and the adenine nucleotide translocase confirms their role in the mitochondrial permeability transition.

A fusion protein between cyclophilin-D (CyP-D) and glutathione S-transferase (GST) was shown to bind to purified liver inner mitochondrial membranes (IMMs) in a cyclosporin A (CsA)-sensitive manner. Binding was enhanced by diamide treatment of the IMMs. Immobilized GST-CyP-D avidly bound a single 30 kDa protein present in Triton X-100-solubilized IMMs; immunoblotting showed this to be the adenine nucleotide translocase (ANT). Binding was prevented by pretreatment of the CyP-D with CsA, but not with cyclosporin H. Purified ANT also bound specifically to GST-CyP-D, but porin did not, even in the presence of ANT.

Interventional study of diltiazem in dilated cardiomyopathy: a report of multiple centre clinical trial in China. Chinese Cooperative Group of Diltiazem Intervention Trial in Dilated Cardiomyopathy.

The aim of this study was to determine the interventional effects of diltiazem on autoantibody mediated myocardial damage in dilated cardiomyopathy (DCM). 221 patients with DCM in 16 hospitals were included in the multiple centre clinical trial from January 1995 to November 1996, using the diltiazem or placebo based on the background therapy for heart failure. Patients were randomly divided into groups for a single blind trial, followed by observation for an average of 7.4 months. After treatment, the heart function of 84% of patients in the diltiazem group recovered to grade I or II, but this occurred for 64% of patients in the placebo group. Heart-thorax ratio was decreased from 0.59+/-0.07 to 0.56+/-0.07 and the left ventricular end-diastolic dimension (LVEDd) from 65.40+/-8.60 mm to 61.12+/-9.86 mm, the left ventricular ejection fraction (EF) was increased from 35.75+/-10.78% to 42.52%+/-11.41% (P<0.01) in the diltiazem group (n=114). The above parameters were not significantly changed in the placebo group (n=107). Mortality was 3.5% in the diltiazem group and 11.2% in the placebo group (P<0.05). Further analysis also shows that LVEDd were reduced and EF were obviously elevated in patients with DCM of LVEDd <70 mm, but the above parameters weren't improved in patients of LVEDd >70 mm. The study suggests that diltiazem is safe and effective in the treatment of DCM, the action mechanism might be intervention in antibody-mediated myocardial damage and protection of myocardium. Diltiazem is suitable for the treatment of the early stage in DCM.

Cardiac cytotoxic mechanism mediated by antibodies against myocardial mitochondrial ADP/ATP carrier in patients with dilated cardiomyopathy.

OBJECTIVE: To investigate mechanism of the antibody-mediated cardiac cytotoxicity and clinical significance in dilated cardiomyopathy (DCM), and study the effects of the antibodies against the myocardial mitochondrial ADP / ATP carrier from sera of patients with dilated cardiomyopathy on the guinea pig ventricular myocytes. PATIENTS AND METHODS: This study included 18 patients with DCM (12 men and 6 women), with mean age of 43 years. Control group included 18 health donors, (9 men and 9 women), with mean age of 32 years. The antibodies against the ADP / ATP carrier and cell membrane 52 000 peptide were examined by immunoblotting. The antibody-mediated cardiac cytotoxicity was studied with the cytotoxic test and whole cell patch-clamp technique. RESULTS: The antibodies against myocardial mitochondrial ADP / ATP carrier and cell membrane 52 000 peptide were positive in 18 patients with DCM, while negative in controls. The antibodies induced cytotoxic damage with time-dependent and enhanced Ca-current in cardiac myocytes. The increasing amplitude of peak Ca(2+)-current was 100 pA-840 pA (n = 8) in different dilution of the antibodies. The effect of the antibodies might be inhibited by verapamil, and were null in controls (n = 4). CONCLUSIONS: The above findings suggest that an increase in the antibody-mediated Ca(2+)-current of cardiac myocytes is related to the cytotoxic damage in dilated cardiomyopathy.

Autoantibodies against ADP/ATP carrier from patients with dilated cardiomyopathy increase activity of voltage-dependent Ca channels in isolated cardiac myocytes.

The effects of autoantibodies against the ADP/ATP carrier, from sera of patients with dilated cardiomyopathy, on calcium channel current (ICa) were studied in enzymatically-isolated guinea pig ventricular myocytes by using a whole cell patch-clamp method. The results showed that the autoantibodies enhanced ICa in a concentration-dependent manner. Verapamil inhibited enhancement of ICa induced by the autoantibodies. Control sera (without the autoantibodies) did not affect ICa. This study suggests that anti-ADP/ATP carrier autoantibodies from sera of patients with dilated cardiomyopathy may enhance ICa and cause calcium overload. Disturbing Ca-channel gating by autoantibodies may contribute to the pathogenesis of dilated cardiomyopathy.

Study of autoantibodies against the adenine nucleotide translocator in idiopathic dilated cardiomyopathy.

The frequency, dynamical change and effects of autoantibodies against the adenine nucleotide translocator (ANT) in idiopathic dilated cardiomyopathy (IDC) were studied. Sera of 16 patients with IDC showed significant binding capacity to the ANT protein (33.3%). Anti-ANT antibody titre was gradually tapered in approx. 2-3 months duration. However, anti-ANT antibody can inhibit the ADP/ATP exchange of heart mitochondria and be organ-specific. Short-term (6 weeks) treatment of 15 anti-ANT antibody-positive IDC patients with prednisone was of beneficial effect. Our results show that autoimmunity to the ANT can contribute to the pathogenesis and/or progression of IDC to a certain extent. But we must pay more attention to the fact that anti-ANT antibody characteristically exists short-term. Therefore, a short-term immunosuppressive treatment should be given to those IDC patients whose anti-ANT antibody is positive.

The role of the ADP/ATP carrier in the pathogenesis of viral heart disease.

The ADP/ATP carrier is an autoantigen in myocarditis and dilated cardiomyopathy, both of which are diseases related to virus infections. Sera of these patients bear carrier-specific autoantibodies inhibiting transmembrane nucleotide transport on isolated mitochondria. To further assess the role of the ADP/ATP carrier in viral heart disease, guinea pigs were immunized with the isolated ADP/ATP carrier protein and A-strain mice were infected with coxsackie B3 virus. Both species generated specific and carrier-inactivating antibodies after immunization/infection. The transport activity of the ADP/ATP carrier-estimated from the cytosolic-mitochondrial difference of the phosphorylation potential of ATP (delta G[cyt-mit])-markedly declined in guinea pig and mice hearts. A close relationship was observed between the magnitude of reduction of delta G(cyt-mit) and the decrease of cardiac function. Therefore, it seems plausible that carrier dysfunction induced by viral infection creates an imbalance in myocardial energy metabolism, and is responsible for the impairment of cardiac function. The underlying mechanism might be an autoimmune reaction triggered via molecular mimicry or a modulation of the expression of ADP/ATP carrier isoforms changing the overall transport capacity of the cardiac ADP/ATP carrier.

[Dynamic observation and significance of autoantibody against ADP/ATP carrier in dilated cardiomyopathy].

The presence and dynamic change of autoantibody against ADP/ATP carrier in patients with dilated cardiomyopathy (DCM) was studied by using indirect micro-solid-phase radioimmunoassay. A significant antibody titre was present in 16 of 48 DCM patients and most of them were in early stage of the disease. The titre of anti-ADP/ATP carrier antibody in DCM patients decreased gradually in a follow-up period of three months. The titre of this antibody in the serum from patients with coronary and rheumatic heart disease were within normal limits. Anti-ADP/ATP carrier antibody may play an important role in the pathogenesis, diagnosis and treatment of DCM.