CONICET | Buscador de Institutos y Recursos Humanos

Chronic Chagas Heart Disease (cChHD) is characterized by high antibody (Ab) levels mainly toward parasite intracellular proteins. Among these, the acidic C-terminal region of the ribosomal P proteins (epitope R13 of TcP2beta) is considered to be highly immunogenic and bears similarity to the second extracellular loop of the beta1-adrenergic receptor (beta1-AR). Our previous results demonstrated that anti-R13 Abs from patients with cChHD recognize and activate beta1-AR and M2-cholinergic receptors, as seen by immunocytochemistry and cAMP accumulation on stably transfected cells. The aim of this work was to evaluate the effect of anti-R13 Ab long-term stimulation on cardiac cells. Thus, adult murine cardiac HL-1 cells were treated with the -AR agonist Isoproterenol (ISO), mAb anti-R13 (17.2), or IgG fractions from cChHD patients. The results showed that ISO produced cell cycle arrest, cellular senescence and apoptosis, and mAb 17.2 induced apoptosis by beta-AR stimulation on cardiac HL-1 cells as seen by TUNEL. Moreover, mAb 17.2 produced an increase in Bax/BclXL ratio mRNA levels. Late apoptosis changes on cardiac cells induced by mAb 17.2 were further confirmed using annexin V-PI dual staining by flow cytometry. Likewise, IgG fractions from cChHD patients produced apoptosis on this cells when compared to IgGs from healthy individuals. These results support the hypothesis that apoptosis caused by anti-R13 Ab chronic stimulation on beta-AR could result in cardiotoxic effects similar to those known to be produced by long term exposure to agonists. This may justify the use of immunoadsorption approaches to avoid the cross-reactive immune response produced by anti-R13 Abs without interfering with anti-parasite immunity.