Anti-beta1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease.
Chronic Chagas heart disease (cChHD), a chronic manifestation of the Trypanosoma cruzi infection, is characterized by high antibody levels against the C-terminal region of the ribosomal P proteins (i.e. peptide R13, EEEDDDMGFGLFD) which bears similarity with the second extracellular loop of beta1-adrenergic receptor (beta1-AR, peptide H26R HWWRAESDEARRCYNDPKCCDFVTNR). Because it has not been demonstrated clearly that IgGs from cChHD patients bind to native human beta1-AR, the aim of this study was to investigate further the physical interaction between cChHD IgGs and the human beta1-AR. Immunofluorescence assays demonstrated the binding of these antibodies to the receptor expressed on stably transfected cells, together with a beta1-AR agonist-like effect. In addition, immunoadsorption of the serum samples from cChHD patients with a commercially available matrix, containing peptides representing the first and the second extracellular loop of the beta1-AR, completely abolished reactivity against the H26R peptide and the physiological response to the receptor. The follow-up of this specificity after in vitro immunoadsorption procedures suggests that this treatment might be used to diminish significantly the serum levels of anti-beta1-AR antibodies in patients with Chagas heart disease.
Labovsky
V
V
Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI), Consejo Nacional de Investigación, Ciencia y Técnica (CONICET), Buenos Aires, Argentina.
Smulski
C R
CR
Gómez
K
K
Levy
G
G
Levin
M J
MJ
D000818:Animals; D000913:Antibodies, Protozoan / Q000378:metabolism*; D001323:Autoantibodies / Q000378:metabolism*; D016466:CHO Cells; D019556:COS Cells; D014355:Chagas Disease / Q000276:immunology*; D002522:Chlorocebus aethiops; D002908:Chronic Disease; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007163:Immunosorbent Techniques; D010446:Peptide Fragments; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D014162:Transfection; D014349:Trypanosoma cruzi / Q000276:immunology
D000913:Antibodies, Protozoan; D001323:Autoantibodies; D007074:Immunoglobulin G; D010446:Peptide Fragments; D018342:Receptors, Adrenergic, beta-1; D000242:Cyclic AMP