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

PABLO ARIAS; LUZ MARÍA RODELES; VICCO MH; PEVERENGO LM; SANCHEZ PUCH SILVIA I; CYMERYNG CB; MARCIPAR I

Congreso; 18° ICE (International Congress of Endocrinology) 2018, 53° annual SEMDSA Congress (Society for Endocrinology, Metabolism and Diabetes of South Africa).; 2018

Society for Endocrinology, Metabolism and Diabetes of South Africa

An altered hypothalamic-pituitary axis (HPA) function has been described in patients with chronic Chagas disease (CCD). Since host reaction to T. cruzi includes β2 adrenergic receptor autoantibodies (anti-β2AR AB), and β2AR are expressed in corticotroph cells, we hypothesized that anti-β2AR AB might contribute to HPA activation in CCD patients. After demonstrating the presence of anti-β2AR AB in these subjects, we performed a bioassay to assess their effects on a cell system expressing β2 receptors, and a cAMP-responsive machinery that stimulates POMC synthesis and release, such as the corticotroph cell line ATt20.Anti-β2AR AB levels were measured in adult CCD patients by an in-house developed ELISA. A subset of positive specimens was selected by their AB titers, and the specific anti-β2AR Ig G fraction was affinity purified. Murine AtT20 cells were transfected with CRE-luc and POMC-luc reporter plasmids (cAMP pathway) and incubated with purified AB. Luciferase activity was compared with results obtained after treatment with clenbuterol (Cb, β2 agonist) or butoxamine (Bu, β2 antagonist). Inactivated anti-β2AR AB and sera from T. cruzi(-) patients served as controls.Anti-β2AR AB induced significant, dose-dependent increases in luciferase activity in relation to negative controls both in CRE-luc (p=0.006) and POMC-luc (p