Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease

Autores
Rodeles Antonelli, Luz María; Vicco, Miguel Hernán; Siano, Alvaro Sebastían; Fuchs, Leonardo Andrés; Peverengo, Luz María; Sanchez Puch, Silvia; Cymeryng, Cora Betriz; Marcipar, Iván Sergio; Arias, Pablo
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Rodeles Antonelli, Luz María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; Argentina
Fil: Vicco, Miguel Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; Argentina
Fil: Siano, Alvaro Sebastían. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina
Fil: Fuchs, Leonardo Andrés. Universidad Nacional del Litoral; Argentina
Fil: Peverengo, Luz María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina
Fil: Sanchez Puch, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Marcipar, Iván Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina
Fil: Arias, Pablo. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Cátedra de Fisiología Humana; Argentina
Materia
ADRENERGIC BETA-2 RECEPTOR AGONIST
ANTIBODIES
CHAGAS DISEASE
CYCLIC AMP
INSULIN RESISTANCE
PITUITARY ADRENOCORTICOTROPIN-SECRETING CELLS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/167595
Acceder
id CONICETDig_6bffdd7f33078584490f49b715274401
oai_identifier_str oai:ri.conicet.gov.ar:11336/167595
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas diseaseRodeles Antonelli, Luz MaríaVicco, Miguel HernánSiano, Alvaro SebastíanFuchs, Leonardo AndrésPeverengo, Luz MaríaSanchez Puch, SilviaCymeryng, Cora BetrizMarcipar, Iván SergioArias, PabloADRENERGIC BETA-2 RECEPTOR AGONISTANTIBODIESCHAGAS DISEASECYCLIC AMPINSULIN RESISTANCEPITUITARY ADRENOCORTICOTROPIN-SECRETING CELLShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Potential 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.Fil: Rodeles Antonelli, Luz María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; ArgentinaFil: Vicco, Miguel Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; ArgentinaFil: Siano, Alvaro Sebastían. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; ArgentinaFil: Fuchs, Leonardo Andrés. Universidad Nacional del Litoral; ArgentinaFil: Peverengo, Luz María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; ArgentinaFil: Sanchez Puch, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Marcipar, Iván Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; ArgentinaFil: Arias, Pablo. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Cátedra de Fisiología Humana; ArgentinaMultidisciplinary Digital Publishing Institute2021-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/167595Rodeles Antonelli, Luz María; Vicco, Miguel Hernán; Siano, Alvaro Sebastían; Fuchs, Leonardo Andrés; Peverengo, Luz María; et al.; Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease; Multidisciplinary Digital Publishing Institute; Pathogens; 10; 3; 3-2021; 1-202076-0817CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2076-0817/10/3/378info:eu-repo/semantics/altIdentifier/doi/10.3390/pathogens10030378info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:41:35Zoai:ri.conicet.gov.ar:11336/167595instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:41:35.486CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease
title Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease
spellingShingle Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease
Rodeles Antonelli, Luz María
ADRENERGIC BETA-2 RECEPTOR AGONIST
ANTIBODIES
CHAGAS DISEASE
CYCLIC AMP
INSULIN RESISTANCE
PITUITARY ADRENOCORTICOTROPIN-SECRETING CELLS
title_short Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease
title_full Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease
title_fullStr Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease
title_full_unstemmed Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease
title_sort Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease
dc.creator.none.fl_str_mv Rodeles Antonelli, Luz María
Vicco, Miguel Hernán
Siano, Alvaro Sebastían
Fuchs, Leonardo Andrés
Peverengo, Luz María
Sanchez Puch, Silvia
Cymeryng, Cora Betriz
Marcipar, Iván Sergio
Arias, Pablo
author Rodeles Antonelli, Luz María
author_facet Rodeles Antonelli, Luz María
Vicco, Miguel Hernán
Siano, Alvaro Sebastían
Fuchs, Leonardo Andrés
Peverengo, Luz María
Sanchez Puch, Silvia
Cymeryng, Cora Betriz
Marcipar, Iván Sergio
Arias, Pablo
author_role author
author2 Vicco, Miguel Hernán
Siano, Alvaro Sebastían
Fuchs, Leonardo Andrés
Peverengo, Luz María
Sanchez Puch, Silvia
Cymeryng, Cora Betriz
Marcipar, Iván Sergio
Arias, Pablo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADRENERGIC BETA-2 RECEPTOR AGONIST
ANTIBODIES
CHAGAS DISEASE
CYCLIC AMP
INSULIN RESISTANCE
PITUITARY ADRENOCORTICOTROPIN-SECRETING CELLS
topic ADRENERGIC BETA-2 RECEPTOR AGONIST
ANTIBODIES
CHAGAS DISEASE
CYCLIC AMP
INSULIN RESISTANCE
PITUITARY ADRENOCORTICOTROPIN-SECRETING CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Rodeles Antonelli, Luz María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; Argentina
Fil: Vicco, Miguel Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; Argentina
Fil: Siano, Alvaro Sebastían. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina
Fil: Fuchs, Leonardo Andrés. Universidad Nacional del Litoral; Argentina
Fil: Peverengo, Luz María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina
Fil: Sanchez Puch, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Marcipar, Iván Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina
Fil: Arias, Pablo. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Cátedra de Fisiología Humana; Argentina
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/167595
Rodeles Antonelli, Luz María; Vicco, Miguel Hernán; Siano, Alvaro Sebastían; Fuchs, Leonardo Andrés; Peverengo, Luz María; et al.; Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease; Multidisciplinary Digital Publishing Institute; Pathogens; 10; 3; 3-2021; 1-20
2076-0817
CONICET Digital
CONICET
url http://hdl.handle.net/11336/167595
identifier_str_mv Rodeles Antonelli, Luz María; Vicco, Miguel Hernán; Siano, Alvaro Sebastían; Fuchs, Leonardo Andrés; Peverengo, Luz María; et al.; Functional autoreactive anti-β2 adrenergic antibodies may contribute to insulin resistance profile in patients with chronic chagas disease; Multidisciplinary Digital Publishing Institute; Pathogens; 10; 3; 3-2021; 1-20
2076-0817
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2076-0817/10/3/378
info:eu-repo/semantics/altIdentifier/doi/10.3390/pathogens10030378
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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