期刊
PATHOGENS
卷 10, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/pathogens10030378
关键词
adrenergic beta-2 receptor agonist; antibodies; chagas disease; insulin resistance; pituitary adrenocorticotropin-secreting cells; cyclic AMP
类别
资金
- Investigation and Innovation Agency of Santa Fe Province (SECTeI)
- National University of Littoral
- CONICET (National Council of Scientific and Technical Investigations)
This study investigated the prevalence of anti-beta 2 adrenergic receptor antibodies in patients with chronic Chagas disease (CCD) and their association with insulin resistance and atherogenic dyslipidemia. The findings suggest that these antibodies may contribute to metabolic disturbances and increase cardiovascular risk in CCD patients.
Potential activation of beta 2 adrenergic receptors (beta 2AR) 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-beta 2AR 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-beta 2AR Abs employing an in vitro bioassay with neuroendocrine cells expressing beta 2AR. A clinical and metabolic evaluation including an OGTT was performed in 80 CCD patients and 40 controls. Anti-beta 2AR Abs were measured by an in-house-developed ELISA, and the beta 2 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-beta 2AR 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 beta 2-agonist effects. Our findings suggest that anti-beta 2AR Abs may induce the activation of beta 2AR 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-beta 2AR Abs could contribute to the pathogenesis of metabolic disturbances described in CCD patients, increasing their cardiovascular risk.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据