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 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.
Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Lucia
L
Ciccoli
Neonatal Intensive Care Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy.
Claudio
C
De Felice
Department of Life Sciences, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Eugenio
E
Paccagnini
Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy ; Child Neuropsychiatry Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
Silvia
S
Leoncini
Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy ; Child Neuropsychiatry Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
Alessandra
A
Pecorelli
Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Cinzia
C
Signorini
Medicine, Surgery and Neurosciences Department, University of Siena, Viale M. Bracci 16, 53100 Siena, Italy.
Giuseppe
G
Belmonte
Clinical Pathology Laboratory Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, Italy ; Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Roberto
R
Guerranti
Child Neuropsychiatry Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, Italy ; Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Alessio
A
Cortelazzo
Department of Life Sciences, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Mariangela
M
Gentile
Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 2, 53100 Siena, Italy ; Child Neuropsychiatry Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
Gloria
G
Zollo
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS/UM1/UM2, BP 14491 34093, Montpellier, Cedex 5, France.
Thierry
T
Durand
Life Science and Biotechnologies, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy ; Department of Food and Nutrition, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Giuseppe
G
Valacchi
Respiratory Pathophysiology and Rehabilitation Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
Marcello
M
Rossi
Child Neuropsychiatry Unit, University Hospital, AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
Joussef
J
Hayek
D000199:Actins / Q000097:blood*; D000293:Adolescent; D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D001321:Autistic Disorder / Q000097:blood* / Q000523:psychology; D002648:Child; D002675:Child, Preschool; D004906:Erythrocyte Count; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000378:metabolism*; D004912:Erythrocytes / Q000473:pathology*; D005260:Female; D006801:Humans; D007360:Intelligence; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D018384:Oxidative Stress
D000199:Actins; D000447:Aldehydes; D008565:Membrane Proteins; C027576:4-hydroxy-2-nonenal