Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical Autism

Autism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily rising in frequency and treatment refractory, where the search for biological markers is of paramount importance. Although red blood cells (RBCs) membrane lipidomics and rheological variables have been report...

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Main Authors: Lucia Ciccoli, Claudio De Felice, Eugenio Paccagnini, Silvia Leoncini, Alessandra Pecorelli, Cinzia Signorini, Giuseppe Belmonte, Roberto Guerranti, Alessio Cortelazzo, Mariangela Gentile, Gloria Zollo, Thierry Durand, Giuseppe Valacchi, Marcello Rossi, Joussef Hayek
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/432616
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author Lucia Ciccoli
Claudio De Felice
Eugenio Paccagnini
Silvia Leoncini
Alessandra Pecorelli
Cinzia Signorini
Giuseppe Belmonte
Roberto Guerranti
Alessio Cortelazzo
Mariangela Gentile
Gloria Zollo
Thierry Durand
Giuseppe Valacchi
Marcello Rossi
Joussef Hayek
author_facet Lucia Ciccoli
Claudio De Felice
Eugenio Paccagnini
Silvia Leoncini
Alessandra Pecorelli
Cinzia Signorini
Giuseppe Belmonte
Roberto Guerranti
Alessio Cortelazzo
Mariangela Gentile
Gloria Zollo
Thierry Durand
Giuseppe Valacchi
Marcello Rossi
Joussef Hayek
author_sort Lucia Ciccoli
collection DOAJ
description Autism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily rising in frequency and treatment refractory, where the search for biological markers is of paramount importance. Although red blood cells (RBCs) membrane lipidomics and rheological variables have been reported to be altered, with some suggestions indicating an increased lipid peroxidation in the erythrocyte membrane, to date no information exists on how the oxidative membrane damage may affect cytoskeletal membrane proteins and, ultimately, RBCs shape in autism. Here, we investigated RBC morphology by scanning electron microscopy in patients with classical autism, that is, the predominant ASDs phenotype (age range: 6–26 years), nonautistic neurodevelopmental disorders (i.e., “positive controls”), and healthy controls (i.e., “negative controls”). A high percentage of altered RBCs shapes, predominantly elliptocytes, was observed in autistic patients, but not in both control groups. The RBCs altered morphology in autistic subjects was related to increased erythrocyte membrane F2-isoprostanes and 4-hydroxynonenal protein adducts. In addition, an oxidative damage of the erythrocyte membrane β-actin protein was evidenced. Therefore, the combination of erythrocyte shape abnormalities, erythrocyte membrane oxidative damage, and β-actin alterations constitutes a previously unrecognized triad in classical autism and provides new biological markers in the diagnostic workup of ASDs.
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spelling doaj-art-55af2528a0d8448c8be64939b8e060dc2025-02-03T01:21:11ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/432616432616Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical AutismLucia Ciccoli0Claudio De Felice1Eugenio Paccagnini2Silvia Leoncini3Alessandra Pecorelli4Cinzia Signorini5Giuseppe Belmonte6Roberto Guerranti7Alessio Cortelazzo8Mariangela Gentile9Gloria Zollo10Thierry Durand11Giuseppe Valacchi12Marcello Rossi13Joussef Hayek14Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyNeonatal Intensive Care Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, ItalyDepartment of Life Sciences, University of Siena, Via A. Moro 2, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyMedicine, Surgery and Neurosciences Department, University of Siena, Viale M. Bracci 16, 53100 Siena, ItalyClinical Pathology Laboratory Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, ItalyChild Neuropsychiatry Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, ItalyDepartment of Life Sciences, University of Siena, Via A. Moro 2, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, ItalyInstitut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS/UM1/UM2, BP 14491 34093, Montpellier, Cedex 5, FranceLife Science and Biotechnologies, University of Ferrara, Via Borsari 46, 44100 Ferrara, ItalyRespiratory Pathophysiology and Rehabilitation Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, ItalyChild Neuropsychiatry Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, ItalyAutism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily rising in frequency and treatment refractory, where the search for biological markers is of paramount importance. Although red blood cells (RBCs) membrane lipidomics and rheological variables have been reported to be altered, with some suggestions indicating an increased lipid peroxidation in the erythrocyte membrane, to date no information exists on how the oxidative membrane damage may affect cytoskeletal membrane proteins and, ultimately, RBCs shape in autism. Here, we investigated RBC morphology by scanning electron microscopy in patients with classical autism, that is, the predominant ASDs phenotype (age range: 6–26 years), nonautistic neurodevelopmental disorders (i.e., “positive controls”), and healthy controls (i.e., “negative controls”). A high percentage of altered RBCs shapes, predominantly elliptocytes, was observed in autistic patients, but not in both control groups. The RBCs altered morphology in autistic subjects was related to increased erythrocyte membrane F2-isoprostanes and 4-hydroxynonenal protein adducts. In addition, an oxidative damage of the erythrocyte membrane β-actin protein was evidenced. Therefore, the combination of erythrocyte shape abnormalities, erythrocyte membrane oxidative damage, and β-actin alterations constitutes a previously unrecognized triad in classical autism and provides new biological markers in the diagnostic workup of ASDs.http://dx.doi.org/10.1155/2013/432616
spellingShingle Lucia Ciccoli
Claudio De Felice
Eugenio Paccagnini
Silvia Leoncini
Alessandra Pecorelli
Cinzia Signorini
Giuseppe Belmonte
Roberto Guerranti
Alessio Cortelazzo
Mariangela Gentile
Gloria Zollo
Thierry Durand
Giuseppe Valacchi
Marcello Rossi
Joussef Hayek
Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical Autism
Mediators of Inflammation
title Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical Autism
title_full Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical Autism
title_fullStr Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical Autism
title_full_unstemmed Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical Autism
title_short Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and β-Actin Alterations: An Unrecognized Triad in Classical Autism
title_sort erythrocyte shape abnormalities membrane oxidative damage and β actin alterations an unrecognized triad in classical autism
url http://dx.doi.org/10.1155/2013/432616
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