Abstract
Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Animals, Newborn
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Antibodies, Protozoan / blood
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Antibodies, Protozoan / immunology
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Antigens, Protozoan / chemistry
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Antigens, Protozoan / immunology*
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Autoantibodies / blood
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Autoantibodies / immunology
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Autoantigens / chemistry
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Autoantigens / immunology*
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Autoimmune Diseases / etiology
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Autoimmune Diseases / immunology*
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Bisoprolol / pharmacology
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Cells, Cultured
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Chagas Cardiomyopathy / etiology
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Chagas Cardiomyopathy / immunology*
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Chagas Disease / blood
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Chagas Disease / complications
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Chagas Disease / immunology
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Cross Reactions
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Immunodominant Epitopes / chemistry
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Immunodominant Epitopes / immunology*
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Leishmania donovani / immunology
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Leishmaniasis / immunology
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Leishmaniasis, Visceral / immunology
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Molecular Mimicry*
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Molecular Sequence Data
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Myocardial Contraction / drug effects
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Myocardium / cytology
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Phosphoproteins / chemistry
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Phosphoproteins / immunology*
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Rats
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Receptors, Adrenergic, beta-1 / chemistry
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Receptors, Adrenergic, beta-1 / immunology*
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Recombinant Proteins / immunology
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Ribosomal Proteins*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Trypanosoma cruzi / immunology*
Substances
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Antibodies, Protozoan
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Antigens, Protozoan
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Autoantibodies
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Autoantigens
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Immunodominant Epitopes
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Phosphoproteins
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Receptors, Adrenergic, beta-1
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Recombinant Proteins
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Ribosomal Proteins
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ribosomal protein P0
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Bisoprolol