Autoreactive anti-beta2 adrenergic antibodies possibly contribute to HPA axis activation in patients with chronic Trypanosoma cruzi infection

ARIAS, PABLO; RODELES, LM; VICCO, MH; PEVERENGO, LM; SANCHEZ PUCH, SILVIA; MERCAU, ME; CYMERYNG, CB; MARCIPAR, I

Cape Town

Congreso; 18th INTERNATIONAL CONGRESS OF ENDOCRINOLOGY; 2018

INTERNATIONAL SOCIETY OF ENDOCRINOLOGY

An alteredhypothalamic-pituitary axis (HPA) function has been described in patients withchronic Chagas disease (CCD). Since host reaction to T. cruzi includes β2 adrenergic receptorautoantibodies (anti-β2AR AB), and β2AR are expressed in corticotroph cells,  wehypothesized that anti-β2AR AB might contribute to HPA activation in CCDpatients. After demonstrating the presence of anti-β2AR AB in these subjects, we performed a bioassay toassess their effects on a cell system expressing β2 receptors, and a cAMP-responsive machinery thatstimulates POMC synthesis and release, such as the corticotroph cell lineATt20.Anti-β2AR AB levels were measured inadult CCD patients by an in-house developed ELISA. A subset of positivespecimens was selected by their AB titers, and the specific anti-β2AR Ig G fraction was affinitypurified.  Murine AtT20 cells were transfected with CRE-luc and POMC-lucreporter plasmids (cAMP pathway) and incubated with purified AB. Luciferaseactivity was compared with results obtained after treatment with clenbuterol(Cb, β2 agonist) orbutoxamine (Bu, β2antagonist). Inactivated anti-β2AR AB and sera from T. cruzi(-) patients served ascontrols.Anti-β2AR AB induced significant,dose-dependent increases in luciferase activity in relation to negativecontrols both in CRE-luc (p=0.006) and POMC-luc (p<0.001) transfected cells,similar to those elicited by Cb. This effect was antagonized by Bu in eachtransfection condition (p=0.026 and <0.001, respectively). Inconclusion, anti-β2ARAB stimulatte β2AR pathways expressed inAtT20 cells and increase POMC expression.  Hence, these antibodiesmight be involved in the pathogenesis of HPA axis activation present inCCD patients