Abstract
Potential activation of β2 adrenergic receptors (β2AR) by specific autoreactive antibodies (Abs) that arise during the host reaction to Trypanosoma cruzi, could contribute to the elevated prevalence of metabolic disturbances described in patients with chronic Chagas disease (CCD). This study aimed to determine the prevalence of anti-β2AR Abs in patients with CCD, as well as the correlation of these Abs with the presence of glucose and lipid metabolism disturbances, in order to explore their association with an insulin resistance profile. Additionally, we tested the functional effects of anti-β2AR Abs employing an in vitro bioassay with neuroendocrine cells expressing β2AR. A clinical and metabolic evaluation including an OGTT was performed in 80 CCD patients and 40 controls. Anti-β2AR Abs were measured by an in-house-developed ELISA, and the β2 adrenergic activity of affinity-purified IgG fractions from patient’ sera were assayed in CRE-Luc and POMCLuc transfected AtT-20 cells. A higher proportion of dysglycemia (72.5% vs. 37.5%; p = 0.001) was observed in the CCD group, accompanied by increased HOMA2-IR (p = 0.019), especially in subjects with Abs (+). Anti-β2AR Abs reactivity (7.01 (2.39–20.5); p = 0.0004) and age >50 years (3.83 (1.30–11.25); p = 0.014) resulted as relevant for IR prediction (AUC: 0.786). Concordantly, Abs (+) CCD patients showed elevated metabolic risk scores and an increased prevalence of atherogenic dyslipidemia (p = 0.040), as compared to Abs (−) patients and controls. On functional bioassays, Abs exerted specific and dose-dependent β2-agonist effects. Our findings suggest that anti-β2AR Abs may induce the activation of β2AR in other tissues besides the heart; furthermore, we show that in patients with CCD these Abs are associated with an insulin resistance profile and atherogenic dyslipidemia, providing biological plausibility to the hypothesis that adrenergic activation by anti-β2AR Abs could contribute to the pathogenesis of metabolic disturbances described in CCD patients, increasing their cardiovascular risk.
Highlights
Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi (T. cruzi) affecting about 8 million people mostly in Latin America
This study aimed to determine the prevalence of anti-β2 adrenergic receptors (β2AR) Abs by enzyme immunoassay in a sample of patients with chronic Chagas disease (CCD), as well as the correlation of these Abs with the presence of glucose and lipid metabolism disturbances in patients in order to explore their association with an insulin resistance profile
As compared to control subjects (CON), no significant differences were observed between the groups regarding age, sex, and body mass index (BMI)
Summary
Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi (T. cruzi) affecting about 8 million people mostly in Latin America. The heterogeneous clinical expression of the disease has been related to the broad spectrum of host–parasite interactions taking place during the chronic infection [2] From this perspective, several mechanisms underlying chronic Chagas disease (CCD) pathogenesis have been described, including tissue damage and inflammatory response due to parasite persistence, autoimmunity, microvascular lesion, and autonomic dysfunction [3]. Parasitic persistence is required for disease development, capable of gathering and maintaining a chronic inflammatory status that would intend to be controlled through mounting a intricate immune response [4] In this context, harmful mechanisms which are not restricted only to direct agent damage, but are related to the degree of immune balance achieved, have become relevant [3]
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