title: Profiling humoral autoimmune repertoire of dilated cardiomyopathy (DCM) patients and development of a disease-associated protein chip.
abstract: Dilated cardiomyopathy (DCM) is a myocardial disease characterized by progressive depression of myocardial contractile function and ventricular dilatation. Thirty percent of DCM patients belong to the inherited genetic form; the rest may be idiopathic, viral, autoimmune, or immune-mediated associated with a viral infection. Disturbances in humoral and cellular immunity have been described in cases of myocarditis and DCM. A number of autoantibodies against cardiac cell proteins have been identified in DCM. In this study, we have profiled the autoantibody repertoire of plasma from DCM patients against a human protein array consisting of 37,200 redundant, recombinant human proteins and performed qualitative and quantitative validation of these putative autoantigens on protein microarrays to identify novel putative DCM specific autoantigens. In addition to analyzing the whole IgG autoantibody repertoire, we have also analyzed the IgG3 antibody repertoire in the plasma samples to study the characteristics of IgG3 subclass antibodies. By combining screening of a protein expression library with protein microarray technology, we have detected 26 proteins identified by the IgG antibody repertoire and 6 proteins bound by the IgG3 subclass. Several of these autoantibodies found in plasma of DCM patients, such as the autoantibody against the Kv channel-interacting protein, are associated with heart failure.
authors.affiliation: Max-Planck-Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Horn
authors.forename: Angelika
authors.initials: A
authors.lastname: Lueking
authors.forename: Derek
authors.initials: D
authors.lastname: Murphy
authors.forename: Alexander
authors.initials: A
authors.lastname: Staudt
authors.forename: Claudia
authors.initials: C
authors.lastname: Gutjahr
authors.forename: Kirsten
authors.initials: K
authors.lastname: Schulte
authors.forename: Andrea
authors.initials: A
authors.lastname: König
authors.forename: Martin
authors.initials: M
authors.lastname: Landsberger
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
authors.forename: Dolores J
authors.initials: DJ
authors.lastname: Cahill
mesh_terms: D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D040081:Protein Array Analysis; D011994:Recombinant Proteins / Q000276:immunology* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C496750:KCNIP1 protein, human; C496752:KCNIP2 protein, human; D051605:Kv Channel-Interacting Proteins; D011994:Recombinant Proteins