Antigenic Targets of Patient and Maternal Autoantibodies in Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose behavioral symptoms become apparent in early childhood. The underlying pathophysiological mechanisms are only partially understood and the clinical manifestations are heterogeneous in nature, which poses a major challenge for diagnosis, prognosis and intervention. In the last years, an important role of a dysregulated immune system in ASD has emerged, but the mechanisms connecting this to a disruption of brain development are still largely unknown. Although ASD is not considered as a typical autoimmune disease, self-reactive antibodies or autoantibodies against a wide variety of targets have been found in a subset of ASD patients. In addition, autoantibodies reactive to fetal brain proteins have also been described in the prenatal stage of neurodevelopment, where they can be transferred from the mother to the fetus by transplacental transport. In this review, we give an extensive overview of the antibodies described in ASD according to their target antigens, their different origins, and timing of exposure during neurodevelopment.

Autoantibody-associated psychiatric symptoms and syndromes in adults: A narrative review and proposed diagnostic approach

“…This supports the heterogeneity of autism’s spectrum immunity mechanisms that underlie a specific immune mechanism responsible for symptom induction. , other serum autoantibodies such as CASPR2, CRMP1 (collapsin response mediator protein 1), and CRMP2 (collapsin response mediator protein 2) have been identified ( Mazon-Cabrera et al., 2019 ) in both autistic patients and the mothers of ASD patients – a finding that supports a potential transfer of maternal antibodies during birth. It is conceivable that these autoantibodies might have an impact on brain development.…”

“…Autism spectrum disorders (ASD) encompass a condition of deficits in social skills in conjunction with repetitive sensory-motor behaviors ( Lord et al., 2018 ). In patients with ASD, autoantibodies against diverse antigens have been identified such as serotonin 5 (5-HT) receptor, human neuron axon filament protein (NAFP), glial fibrillic acid protein (GFAP), GAD65 and ganglioside-monosialic acid (GM1) antibodies ( Mazon-Cabrera et al., 2019 ). This supports the heterogeneity of autism’s spectrum immunity mechanisms that underlie a specific immune mechanism responsible for symptom induction.…”

Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

“…Subsequent studies were able to establish what proteins corresponded to these 37/39kDa and 72kDa bands, representing a critical step in maternal autoantibody related autism research [50,63,64]. Braunschweig et al's seminal study [63] showed that the most common proteins to exhibit reactivity exclusively to these maternal autoantibodies were lactate dehydrogenase A and B (LDH-A, LDH-B), involved in neuronal and astrocytic metabolism and long-term memory [65], collapsing response mediator proteins 1 and 2 (CRMP1 and CRMP2), responsible for correct cell migration [66] and stress-induced phosphoprotein 1 (STIP1), important in neuronal survival and dendritic arborization [63,67,68]. Importantly, all the other identified antigens were also expressed in high quantities in the foetal brain and had key roles in neurodevelopment [50,63].…”

Maternal Diabetes Induces Immune Dysfunction in Autistic Offspring Through Oxidative Stress in Hematopoietic Stem Cells

“…During the past few decades, the prevalence of ASD has significantly increased to a ratio of 1:59 in the United States ( 1 – 3 ). Many factors, including genetics/epigenetics, environmental risk factors, sex, and immune system ( 4 ), have been reported to contribute to ASD development, while the detailed mechanism remains largely unclear ( 3 , 5 – 7 ).…”