Interaccion de autoanticuerpos chagasicos con el tercer dominio extracelular del receptor muscarinico cardiaco humano: implicancias funcionales y patologicas / Interaction of chagasic autoantibodies with the third extracellular domain of the human heart muscarinic receptor: functional and pathological implications

Este trabajo demuestra, en pacientes chagásicos, la presencia de auto-anticuerpos circulantes reactivos contra el tercer dominio extracelular del receptor muscarínico M2, humano utilizando un péptido sintético correspondiente a la secuencia 169-192 del receptor, mediante técnicas de ELISA e immunoblotting. Anticuerpos anti-péptido purificados por inmunoafinidad revelaron actividad muscarínica cardíaca, ya que deprimieron la contractilidad, inhibieron la producción de AMPc e incrementaron los niveles de GMPc; estos efectos fueron bloqueados específicamente por el péptido sintético y por atropina. Comprobamos una fuerte asociación entre presencia de autoanticuerpos anti-péptido M2 y manifestaciones de disautonomia en los pacientes, sugiriendo su posible utilidad como marcadores tempranos de disautonomia.

Experimental autoimmune myocarditis: a suitable model to study neuroimmune crosstalk

This review regards the main functional characteristics of hearts subjected to an autoimmune response focusinf especially on the role of T lymphocytes and autoantibodies in the development of cardiac dysfunction. Evidence of a strong association in the onset and time-course of immune response and cardiac dysfunction is presented and the results are viewed comparatively with myocarditis models induced by heart, parasite or virus inoculation. Cardiac damage is evaluated regarding various aspects, namely histologic, immunologic, biochemical, pharmacologic, physiologic. Finally, the model, for its characteristics of resulting from an autoimmune response against the heart with functional consequences, has proved its usefulness to study neuroimmune interaction, mainly the immune to nervous direction, as autoantibodies and T cell-derived factors have a role in cardiac failure.