Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, andβ-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 membraneβ-actin protein was evidenced. Therefore, the combination of erythrocyte shape abnormalities, erythrocyte membrane oxidative damage, andβ-actin alterations constitutes a previously unrecognized triad in classical autism and provides new biological markers in the diagnostic workup of ASDs.

Ultraviolet radiation and free radical damage to skin

Solar UVB (290-320 nm) and particularly UVA (320-380 nm) radiations have a capacity to generate reactive chemical species, including free radicals, in cells. These intermediates have been shown to be involved in various biological effects in cultured human skin cells (e.g. cell death) and skin (e.g. erythema). Endogenous glutathione is a critical molecule in protection against the cytotoxic effects of both wavelength ranges. Although there is evidence from cellular studies for the involvement of an oxidative component of UVC/UVB radiations in activation of several genes, the doses used are generally extremely cytotoxic and could cause aberrant signalling. Genes activated by sublethal doses of UVA radiations (e.g. haem oxygenase 1 and the CL100 phosphatase) are clearly redox regulated. The strong induction of haem oxygenase 1 in human fibroblasts has been implicated in an adaptive response to oxidative membrane damage that involves increased synthesis of the iron storage protein, ferritin.