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

RODELES, LM; SANCHEZ PUCH, S; VICCO, MH; CABRERA, G; PEVERENGO, LM; MERCAU, ME; CYMERYNG, CB; MARCIPAR, I; ARIAS, P

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC-SAIB-SAI-SAA-SAB-SAB-SAFE-SAFIS-SAH-SAP

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 mightplay a pathogenic role in these alterations. After demonstratingthe presence of anti-β2AR AB inpatients 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 byELISA.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 luciferaseactivityin relation to negative controls both in CRE-luc (p=0.006) andPOMC-luc (p<0.001) transfected cells, similar to those elicited byCb. Furthermore, this effect was antagonized by Bu in each transfectioncondition (p=0.026 and <0.001, respectively). The observedstimulation showed dose-dependent characteristics.Our results indicate that anti-β2AR AB exert an agonist effect onβ2AR pathways expressed in AtT20 cells, lending biologic plausibilityto the hypothesis that these antibodies may contribute to thepathogenesis of metabolic disturbances in CCD patients. Studies onthe effects of anti-β2AR AB performedin hepatic cell systems are inprogress to answer this question.