Apoptosis induced by antibodies against T. cruzi ribosomal P proteins on cardiac cells

LEVY G; LABOVSKY V; GOMEZ K; LEVIN MJ

Rio de Janeiro, Brasil

Congreso; 13th International Congress of Immunology, ImmunoRio.; 2007

ALAI, SBI (Sociedade Brasileira de Imunologia)

Chronic Chagas Heart Disease (cChHD), a chronic manifestation of the Trypanosoma cruzi (T. cruzi) infection, is characterized by high antibody (Ab) levels mainly toward parasite intracellular proteins. Among these, the acidic C-terminal region of the ribosomal P proteins (i.e. epitope R13 of TcP2b protein) is considered to be highly immunogenic and bears similarity with the second extracellular loop (H26R) of the b1-adrenergic receptor (b1-AR). Our previous results demonstrated that anti-R13 antibodies from patients with cChHD recognize and activate the b1-AR, as seen by immunocytochemistry and cAMP accumulation on b1-AR stably transfected cells. Furthermore, monoclonal anti-R13 Abs were able to induce 6.37% ± 2.29 of apoptosis on cardiac HL-1 cells, as seen by terminal deoxynucleotidyl transferase-mediated UTP end labeling reactivity (TUNEL), while non-relevant Ab produced only a 0.72% ± 0.92 of apoptosis. This long term induction was completely abolished by preincubation with the b-AR antagonist propranolol (1.33% ± 1.08), suggesting that apoptosis was induced by b-AR stimulation. Interestingly, immunoadsorption of serum samples from cChHD patients with a commercially available matrix containing peptides representing the first and the second extracellular loop of the b1-AR (Coraffin from Fresenius Medical Care Affina GmbH, Berlin, Germany) completely abolished their reactivity against H26R peptide and their functional effect on the receptor. These data not only contribute to understand the mechanisms underlying the cardiac physiopathology of the Chagas Disease, but also suggest that the removing of anti-b1-AR Abs by immunoadsorption may perhaps be an additional therapeutic tool for cChHD patients.