FUNCTIONAL EFFECTS OF ANTI-B2 ADRENERGIC AUTOANTIBODIES FROM PATIENTS WITH CHRONIC CHAGAS DISEASE IN A CORTICOTROPH CELL LINE

SANCHEZ PUCH, SILVIA; PEVERENGO, LUZ; VICCO, MIGUEL; MARCIPAR, IVAN; MERCAU, MARÍA ELISA; ARIAS, PABLO; RODELES, LUZ; CABRERA, GABRIEL; CYMERYNG, CORA

Ciudad Autónoma de Buenos Aires

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Inmunología, Sociedad Argentina de Parasitología, entre otros.

Inflammation associated with parasite persistence in adipose tissue,resulting in altered adiponectin/resistin levels, has been heldresponsible for the higher prevalence of obesity and diabetes describedin patients with chronic Chagas disease (CCD). Since hostreaction to T. cruzi includes β2 adrenergic receptor autoantibodies(anti-β2AR AB), and β2AR are expressed in metabolically activetissues (liver, fat), we hypothesized that anti-β2AR AB might play a pathogenic role in these alterations. After demonstratingthe presence of anti-β2AR AB in patients with CCD, we aimedto perform a bioassay to assess their functional effects on a cellsystem expressing β2 receptors and a cAMP-responsive machinery.Anti-β2AR AB levels were measured in adult CCD patients by ELISA.A subset of positive specimens was selected by their AB titers,and specific anti-β2AR Ig G fraction were affinity purified. MurineAtT20 cells were transfected with CRE-luc and POMC-luc reporterplasmids (cAMP pathway) and incubated with purified AB. Luciferaseactivity was compared with results obtained after treatment withclenbuterol (Cb, β2 agonist) or butoxamine (Bu, β2 antagonist). Inactivatedanti-β2AR AB and sera from T. cruzi(-) patients served ascontrols.Anti-β2AR AB induced significant increases in luciferase activityin relation to negative controls both in CRE-luc (p=0.006) andPOMC-luc (p