Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Sera from patients with chronic Chagas heart disease recognize the carboxyl-terminal regions of the Trypanosoma cruzi ribosomal P proteins defined by B cell epitopes P013 (EDDDDDFGMGALF) and R13 (EEEDDDMGFGLFD) corresponding to the T. cruzi ribosomal P0 (TcP0) and P2β (TcP2β) proteins, respectively. It has been hypothesized that both epitopes may induce antibodies that cross-react and stimulate the β1-adrenoreceptor. However, no proof as to their pathogenicity has been obtained. We investigated the consequences of immunizing mice with either TcP0 or TcP2β proteins. Of 24 immunized animals, 16 generated antibodies against the carboxyl-terminal end of the corresponding protein, 13 of which showed an altered ECG (P<0.001, 81%). Immunization with TcP0 induced anti-P013 antibodies that bind to and stimulate cardiac G-protein-coupled receptors and are linked to the induction of supraventricular arrhythmia, repolarization, and conduction abnormalities as monitored by serial electrocardiographic analysis. In contrast, immunization with TcP2β generated anti-R13 antibodies with an exclusive β1-adrenergic-stimulating activity whose appearance strictly correlated with the recording of supraventricular tachycardia and death. These findings demonstrate that anti-P antibodies are arrhythmogenic in the setting of a normal heart, since no inflammatory lesions or fibrosis were evident to light microscopic examination.

Registro:

Documento: Artículo
Título:Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic
Autor:Lopez Bergami, P.; Scaglione, J.; Levin, M.J.
Filiación:Lab. Biol. Molec. Enferm. de Chagas, INGEBI, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:β1-adrenoreceptor; Arrhythmia; Chagas disease; G-protein-coupled receptors; Supraventricular tachycardia; beta 1 adrenergic receptor; cross reacting antibody; G protein coupled receptor; glycine cleavage system; immunoglobulin G; protozoon antibody; ribosome protein; synthetic peptide; adolescent; animal cell; animal model; antigenicity; arrhythmogenesis; article; carboxy terminal sequence; Chagas disease; controlled study; electrocardiography; epitope mapping; heart arrhythmia; human; humoral immunity; immunization; mouse; nonhuman; pathogenicity; priority journal; supraventricular tachycardia; Trypanosoma cruzi; Alanine; Amino Acid Sequence; Animals; Antibodies, Protozoan; Antibody Formation; Carrier Proteins; Chagas Cardiomyopathy; Cloning, Molecular; COS Cells; Electrocardiography; Epitope Mapping; Glutathione Transferase; Heart Rate; Humans; Immunization; Immunoglobulin G; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Mutagenesis; Myocardium; Protozoan Proteins; Rats; Recombinant Fusion Proteins; Ribosomal Proteins; Trypanosoma cruzi; Animalia; Protozoa; Trypanosoma; Trypanosoma cruzi
Año:2001
Volumen:15
Número:14
Página de inicio:2602
Página de fin:2612
DOI: http://dx.doi.org/10.1096/fj.01-0132com
Título revista:FASEB Journal
Título revista abreviado:FASEB J.
ISSN:08926638
CODEN:FAJOE
CAS:Alanine, 56-41-7; Antibodies, Protozoan; Carrier Proteins; Glutathione Transferase, EC 2.5.1.18; Immunoglobulin G; L12E protein, Trypanosoma cruzi; maltose-binding protein; Protozoan Proteins; Recombinant Fusion Proteins; Ribosomal Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08926638_v15_n14_p2602_LopezBergami

Referencias:

  • Elizari, M.V., Chiale, P.A., Pharmacologic treatment of arrhythmias related to chronic Chagas heart disease (2000) Arrhytmia Management in Chagas Disease, pp. 95-116. , (Tentori, M. C., Segura, E., and Hayes, D. L., eds), Futura Publishing Company, Armonk, New York
  • Halperin, C., Rassi, S., Clinical relevance of invasive electrophysiologic studies in patients with Chagas disease (2000) Arrhytmia Management in Chagas Disease, pp. 83-94. , (Tentori, M.C., Segura, E., and Hayes, D.L., eds), Futura Publishing Company, Armonk, New York
  • Levin, M.J., Kaplan, D., Ferrari, I., Arteman, P., Vazquez, M., Panebra, A., Humoral autoimmune response in Chagas disease: Trypanosoma cruzi ribosomal antigens as immunizing agents (1993) FEMS Immunol. Med. Microbiol., 7, pp. 205-210
  • Brandariz, S., Schijman, A., Vigliano, C., Arteman, P., Viotti, R., Beldjord, C., Levin, M.J., Detection of parasite DNA in Chagas heart disease (1995) Lancet, 346, pp. 1370-1371
  • Levin, M.J., Mesri, E., Benarous, R., Levitus, G., Schijman, A., Levy-Yeyati, P., Chiale, P., Segura, E.L., Identification of major Trypanosoma cruzi antigenic determinants in chronic Chagas' heart disease (1989) Am. J. Trop. Med. Hyg., 41, pp. 530-539
  • Mesri, E., Levitus, G., Hontebeyrie-Joskowicz, M., Dighiero, G., Van Regenmortel, M.H.V., Levin, M.J., Major Trypanosoma cruzi determinant in Chagas' heart disease shares homology with the systemic lupus erythematosus ribosomal P protein epitope (1990) J. Clin. Microbiol., 28, pp. 1219-1224
  • Levitus, G., Hontebeyrie-Joskowicz, M., Van Regenmortel, M.H.V., Levin, M.J., Humoral autoimmune response to ribosomal P proteins in chronic Chagas' heart disease (1991) Clin. Exp. Immunol., 85, pp. 413-417
  • Skeiky, J., Benson, D.R., Parsons, M., Elkon, K.B., Reed, S.D., Cloning and expression of Trypanosoma cruzi acidic ribosomal PO protein and epitope analysis of anti-PO autoantibodies in Chagas' disease patients (1992) J. Exp. Med., 176, pp. 201-211
  • Aznar, C., Lopez Bergami, P., Brandariz, S., Mariette, C., Liegeard, P., De Deus Alves, M.C., Luna Barreiro, E., Hontebeyrie-Joskowicz, M., Prevalence of anti-R13 antibodies in human Trypanosoma cruzi infection (1995) FEMS Immunol. Med. Microbiol., 12, pp. 231-238
  • Ferrari, I., Levin, M.J., Wallukat, G., Elies, R., Lebesgue, D., Chiale, P., Elizari, M., Hoebeke, J., Molecular mimicry between the immunodominant ribosomal protein PO of Trypanosoma cruzi and a functional epitope on the human β1-adrenergic receptor (1995) J. Exp. Med., 182, pp. 59-65
  • Kaplan, D., Ferrari, I., Lopez Bergami, P., Mahler, E., Levitus, G., Chiale, P., Hoebeke, J., Levin, M.J., Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in Lupus (1997) Proc. Natl. Acad. Sci., 94, pp. 10301-10306
  • Elies, R., Ferrari, I., Wallukat, G., Lebesgue, D., Chiale, P., Elizari, M., Rosenbaum, M., Levin, M., Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with Chagas' disease (1996) J. Immunol., 157, pp. 4203-4211
  • Masuda, M., Levin, M.J., Farias de Oliveira, S., Dos Santos Costa, P., Lopez Bergami, P., Couiri Pedrosa, R., Ferrari, I., Campos De Carvalho, A., Functionally active cardiac antibodies in Chronic Chagas disease are specifically blocked by Trypanosoma cruzi antigens (1998) FASEB J., 12, pp. 1551-1558
  • Chiale, P.A., Ferrari, I., Mahler, E., Vallazza, M.A., Elizari, M.V., Rosenbaum, M.B., Levin, M.J., Differential profile and biochemical effects of antiautonomic membrane receptor antibodies in ventricular arrhythmias and sinus node dysfunction (2001) Circulation, 103, pp. 1765-1771
  • Sadigursky, M., Andrade, S.G., Electrocardiographic changes in experimental chronic murine Chagas' disease (1986) Braz. J. Med. Biol. Res., 19, pp. 379-388
  • Andrade, S.G., Sadigursky, M., The conduction system of the heart in mice chronically infected with Trypanosoma cruzi: Histopathological lesions and electrocardiographic correlations (1987) Mem. Inst. Osw. Cruz., 82, pp. 59-66
  • Postam, M., Bailey, J., Dvorak, J., McDaniel, J., Pottala, E., Studies of Trypanosoma cruzi clones in inbred mice III. Histopathological and electrocardiographic responses to chronic infection (1987) Am. J. Trop. Med. Hyg., 37, pp. 541-549
  • Teixeira, A.R.L., Teixeira, M.L., Santos-Buch, C.A., The immunology of experimental Chagas disease. IV. Production of lesions in rabbits similar to those of chronic Chagas disease in man (1975) Am. J. Pathol., 80, pp. 163-179
  • Lopetegui, R., Sosa Miatello, C., Fiorotto, E.R., Trypanosoma cruzi and mouse myocardium ribosomes. Antibody detection in experimental Chagas infection (1983) Commun. Biol., 2, pp. 79-85
  • Lopetegui, R., Sosa Miatello, C., Fiorotto, E.R., Anti-ribosome humoral antibodies elicited in Trypanosoma cruzi infected mice (1983) Commun. Biol., 2, pp. 195-202
  • Ruiz, A.M., Esteva, M., Cabeza Meckert, P., Laguens, R.P., Segura, E.L., Protective immunity and pathology induced by inoculation of mice with different subcellular fractions of Trypanosoma cruzi (1985) Acta Tropica, 42, pp. 299-309
  • Lopez Bergami, P., Cabeza Meckert, P., Kaplan, D., Levitus, G., Elias, F., Quintana, F., Van Regenmortel, M., Levin, M.J., Immunization with recombinant Trypanosoma cruzi ribosomal P2β protein induces changes in the electrocardiogram of immunized mice (1997) FEMS Immunol. Med. Microbiol., 18, pp. 75-85
  • Schijman, A.G., Levitus, G., Levin, M.J., Characterization of the C-terminal region of a T. cruzi 38-kDa ribosomal PO protein that does not react with lupus anti-P autoantibodies (1992) Immunol. Lett., 33, pp. 15-20
  • Tekiel, V.S., Mirkin, G.A., Gonzalez Cappa, S.M., Chagas' disease: Reactivity against homologous tissues induced by different strains of Trypanosoma cruzi (1997) Parasitology, 115, pp. 495-502
  • Pilgrim, H., DeOme, K., Intraperitoneal pentobarbital anesthesia in mice (1955) Exp. Med. Surg., 13, pp. 401-403
  • Muller, S., Couppez, M., Briand, J.P., Gordon, J., Sautiére, P., Van Regenmortel, M.H.V., Antigenic structure of histone H2B (1985) Biochim. Biophys. Acta, 827, pp. 235-246
  • Levin, M.J., Vazquez, M., Kaplan, D., Schijman, A., The Trypanosoma cruzi ribosomal P protein family: Classification and antigenicity (1993) Parasitol. Today, 9, pp. 381-384
  • Palczewski, K., Kumasaka, T., Hori, T., Behnke, C.A., Motoshima, H., Fox, B.A., Le Trong, I., Miyano, M., Crystal structure of rhodopsin: A G protein-coupled receptor (2000) Science, 289, pp. 739-745
  • Goldbarg, A.N., Hellerstein, H.K., Bruell, J.H., Daroczy, A.F., Electrocardiogram of the normal mouse, Mus musculus: General considerations and genetic aspects (1968) Cardiovasc. Res., 2, pp. 93-99
  • Kishimoto, C., Matsumori, A., Ohmae, M., Tomioka, N., Kawai, C., Electrocardiographic findings in experimental myocarditis in DBA/2 mice: Complete atrioventricular block in the acute stage, low voltage of the QRS complex in the subacute stage and arrhythmias in the chronic stage (1984) J. Am. Coll. Cardiol., 3, pp. 1461-1468
  • Borda, E., Sterin-Borda, L., Antiadrenergic and muscarinic receptor antibodies in Chagas' cardiomyopathy (1996) Int. J. Cardiol., 54, pp. 149-156
  • Kierszenbaum, F., Chagas' disease and the autoimmunity hypothesis (1999) Clin. Microbiol. Rev., 12, pp. 210-223
  • Rose, N.R., Bona, C., Defining criteria for autoimmune diseases (Witebsky's postulates revisited) (1993) Immunol. Today, 14, pp. 426-430
  • Tomita, M., Spinale, F.G., Crawford, F.A., Zile, M., Changes in left ventricular volume, mass, and function during the development and regression of supraventricular tachycardia-induced cardiomyopathy (1991) Circulation, 83, pp. 635-644
  • Matsui, S., Fu, M., Katsuda, S., Hayase, M., Yamaguchi, N., Teraoka, K., Kurihara, T., Hjalmarson, A., Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits (1997) J. Mol. Cell. Cardiol., 29, pp. 641-655
  • Tarleton, R.L., Zhang, L., Chagas disease etiology: Autoimmunity or parasite persistence? (1999) Parasitol. Today, 15, pp. 94-99
  • Schijman, A., Vigliano, C., Burgos, J., Favaloro, R., Perrone, S., Laguens, R., Levin, M.J., Early diagnosis of recurrence of Trypanosoma cruzi infection by polymerase chain reaction after heart transplantation of a chronic Chagas' heart disease patient (2000) J. Heart Lung Transpl., 19, pp. 1114-1117
  • Mahler, E., Sepulveda, P., Jeannequin, O., Liegeard, P., Gounon, P., Wallukat, G., Eftekhari, P., Hontebeyrie, M., A monoclonal antibody against the immunodominant epitope on the ribosomal P2β protein of Trypanosoma cruzi interacts with the human β1-adrenergic receptor (2001) Eur. J. Immunol., 31, pp. 2210-2216
  • Gehrmann, J., Berul, C.I., Cardiac electrophysiology in genetically engineered mice (2000) J. Cardiovasc. Electrophysiol., 11, pp. 354-368

Citas:

---------- APA ----------
Lopez Bergami, P., Scaglione, J. & Levin, M.J. (2001) . Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic. FASEB Journal, 15(14), 2602-2612.
http://dx.doi.org/10.1096/fj.01-0132com
---------- CHICAGO ----------
Lopez Bergami, P., Scaglione, J., Levin, M.J. "Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic" . FASEB Journal 15, no. 14 (2001) : 2602-2612.
http://dx.doi.org/10.1096/fj.01-0132com
---------- MLA ----------
Lopez Bergami, P., Scaglione, J., Levin, M.J. "Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic" . FASEB Journal, vol. 15, no. 14, 2001, pp. 2602-2612.
http://dx.doi.org/10.1096/fj.01-0132com
---------- VANCOUVER ----------
Lopez Bergami, P., Scaglione, J., Levin, M.J. Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic. FASEB J. 2001;15(14):2602-2612.
http://dx.doi.org/10.1096/fj.01-0132com